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The resurgence of congenital syphilis: A cocaine-related problem
The resurgence of congenital syphilis: A cocaine-related problem C o n s o l a c i o n G. Sison, MD, Enrique M. Ostrea, Jr., MD, Milagros P. Reyes, MD, a n d Valiollah Salari, PhD From the Departments of Pediatrics, Medicine and Obstetrics and Gynecology, Hutzel Hospital and Wayne State University, Detroit, Michigan The relationship of maternal illicit drug use to congenital syphilis was studied in a population of newborn infants (N = 1012) who were screened for intrauterine exposure to illicit drugs by meconium analysis and whose mothers were screened for syphilis by the rapid plasmin reagin fluorescent treponemal antibody, absorbed (RPR/FTA-ABS) test. The result of the meconium drug screening was positive in 449 (44.3%) infants: 401 (39.6%) screening results were positive for cocaine, 71 (7%) positive for opiate, and 31 (3. I%) positive for cannabinoid. The maternal RPR/FTA-ABS result was positive in 72 (7. I%) women, and congenital syphilis was diagnosed in 46 (4.5%) infants on the basis of Centers for Disease Control and Prevention definitions. The incidence of positive RPR/FTA-ABS result (10.5% vs 4.4%) and congenital syphilis (7% vs 2.5%) was significantly higher (p <0.01) among infants with positive results compared with those with negative drug screening results. Similarly, the incidence of positive RPR/FTA-ABS (I I% vs 4.6%) and congenital syphilis (8% vs 2.3%) was significantly (p <.0.01) higher among infants with cocaine-positive results compared with those with cocaine-negative results. We conclude that maternal illicit drug use, specifically cocaine, is significantly related to the resurgence of congenital syphilis among newborn infants. (J Pediatr 1997;130:289-2)
The number of women who use illicit drugs during pregnancy has increased in the last few years.l, 2 During the same period an increase in the incidence of primary and secondary syphilis was also observed among women of child-bearing age, 3-5 resulting in an increase in the incidence of congenital syphilis.6 These trends have been ascribed to drug abuse, particularly cocaine abuse. 7-10 A correlation between congenital syphilis and maternal drug use has been suggested in two retrospective studies, 11, 12 both of which determined drug use by maternal serf-report or urine toxicology. However, these methods have low sensitivity for drag detection2; consequently, a large number of drug-exposed infants may Presented in part at the Society for Pediatric Research Meeting, May 4-7, 1992, Baltimore, Maryland. Submitted for publication Feb. 13, 1996; accepted Sept. 5, 1996. Reprint requests: Enrique M. Ostrea, Jr., MD, Department of Pediatrics, Hutzel Hospital, 4707 St. Antoine, Detroit, MI 48201. Copyright © 1997 by Mosby-Year Book, Inc. 0022-3476/97/$5.00 + 0 9/21/77831
not be detected. The risk of the latter group to congenital syphilis has not been assessed. Meconium drag analysis is a new and sensitive test to detect infants who have been gestationally exposed to drugs, 2, 13 and with its use, a larger number of drug-exposed infants can be identified. This is a retrospective review of 1012 infants FFA-ABS RPR
Fluorescenttreponemal antibody, absorbed Rapidplasmin reagin
who had been previously tested for drugs by meconium drug analysis to ascertain any correlation between syphilis/positive rapid plasmin reagin serologic test results and maternal substance abuse. METHODS The meconium drug test is used in our nursery to screen infants who are suspected of having been antenatally exposed to illicit drugs, specifically to cocaine, opiate, or cannabinoid. These include infants with the following risk
289
290
Sison et al.
The Journal of Pediatrics February 1997
Table I. Association of meconium drug screening with maternal serology or congenital syphilis (+) Serology Meconium drug screening Drug screening Negative Positive Cocaine Negative Positive Opiate Negative Positive Cannabinoid Negative Positive
(+) Syphilis
No.
(%)
p*
No.
(%)
p*
25 47
(4.4) (10.5)
0.0002
14 32
(2.5) (7.1)*
0.0004
28 44
(4.6) (11.0)
0.0001
14 32
(2.3) (8.0)
0.0002
67 5
(7.1) (7.0)
0.980
45 1
(4.8) (1.4)
0.194
70 2
(7.1) (6.5)
0.884
45 l
(4.6) (3.2)
0.719
+, Positiveresult. *Pearson chi-squareanalysis(negativevs positivegroups).
factors: (1) maternal history of cocaine, opiate, or marijuana use in the current or past pregnancy, (2) maternal history of alcohol use, defined as the consumption of at least 200 ml of an alcoholic beverage, 3 to 4 times per week, (3) poor maternal prenatal care defined as <2 prenatal visits for the entire pregnancy, (4) signs of drug withdrawal in the infant with negative maternal drug history, (5) abruptio placentae or positive result of human immunodeficiency virus screening in the mother, and (5) social risk factors, such as infant for adoption, home delivery, or teenage pregnancy. All parturients in our hospital are also routinely screened for syphilis by the RPR test, and if results are positive, are tested further by the fluorescent, treponemal, antibody absorption test. Infants who had a meconium drug test done during a select 10-month period were enrolled in the study. The medical records of the infant and mother were reviewed to determine the results of the meconium drag test, the reason(s) for drug testing, the results of the maternal serologic test for syphilis, and to verify the diagnosis of congenital syphilis on the basis of the Centers for DiseaseControl and Prevention definitions.14 Pertinent demographic and clinical data on mother and infant were obtained from the chart. No parental consent was obtained for the chart review; however, the confidentiality of the information derived from the chart review was strictly maintained. Data analysis included Pearson chi-square analysis and odds ratio for cross-tabulated data, Student t test for comparison of means, and stepwise, logistic regression to predict a dichotomous outcome variable from two or more other predictor variables. A value o f p <0.05 was used as the level of statistical significance.
RESULTS During the 10-month study period, 1012 infants who had drug testing were enrolled (52% girls, 48% boys). The mean
(SD) gestational age was 37.6-+ 3.2 weeks, length 45.5 + 15.1 cm, birth weight 2701.9 -+ 708.2 gm, and head circumference 31.9 + 8.7 cm. For the mothers, 82% were single, 85% were black women, 12.1% were white women, and 28.9% admitted to opiate or cocaine use during the present pregnancy. Based on the reasons for drug testing, 363 (35.9%) infants had a meconium drug test because of maternal history of current use of cocaine or opiate, 43 (4.2%) because of maternal illicit drug use only in the past, 133 (13.1%) because of maternal alcohol use or marijuana use, 263 (26%) because of poor maternal, prenatal care, 84 (8.3%) because of signs of withdrawal in the infant, abruptio placentae, or human immunodeficiency virus infection in the mother, and 76 (7.5%) because of social risk factors. In 50 (5%) infants, the reason for drug testing was not specified in the chart. In many instances, this may be because of a high-risk condition in the mother (e.g, single mother with multiple partners or history of other sexually transmitted diseases such as herpes simplex or hepatitis B). The results of the drugs test on 1012 infants were as follows: 449 (44.3%) were positive for any drug, 401 (39.6%) were positive for cocaine, 71 (7%) positive for opiate, and 31 (3.1%) positive for cannabinoid. The drug positivity rate was highest (83%) among infants whose mothers were current users of drugs (cocaine or opiate). However, 47% of infants whose mothers admitted only to drug use in the past or 27% of infants whose mothers admitted only to alcohol or marijuana use also had positive screening results for cocaine or opiate. Among the mothers with poor prenatal care (N = 263), 15.2% had positive results for cocaine, 1.9% had positive results for opiate, and 1.5% had positive results for cannabinoids. Seventy-two mothers (7.1%) had a positive serologic re-
The Journal of Pediatrics Volume 130, Number 2
sult (RPR/FTA-ABS), and congenital syphilis was diagnosed in 46 infants (4.5%), primarily as a result of inadequate maternal treatment. However, two infants had clinical signs of congenital syphilis (e.g., hepatosplenomegaly and/or long bone metaphyseal radiolucencies). The association of the meconium drug screen results with maternal RPR/FTA-ABS results and congenital syphilis is shown in Tables I and II, respectively. The incidence and relative risk of a positive serology result or congenital syphilis were significantly high among infants with a positive meconium drug screen result or those whose results were positive for cocaine. However, forward, stepwise logistic regression of the following variables--cocaine, meconium drug screen, opiate, and cannabinoid--showed that only the positive cocaine test result was significantly (p <0.001) predictive of a positive serologic result or congenital syphilis. When controlling for alcohol use, a positive drug screen result for cocaine was still significantly associated with a positive serologic result (11% vs 4.7%, p <0.001 by Pearson chi-square; odds ratio = 2.5, confidence interval 1.5 to 4.2) or congenital syphilis (8.0% vs 2.2%, p <0.0001 by Pearson chi-square, odds ratio = 3.9, confidence interval 1.9 to 7.9). Among mothers who had a positive serology resuk for syphilis, the risk of cocaine use was significantly increased (odds ratio of 2.56, 95% confidence interval 1.57 to 4.19, p <0.0001). Similarly, among infants in whom congenital syphilis was diagnosed, the risk of cocaine use in their mothers was also increased (odds ratio 3.69, 95% confidence interval 1.94 to 7.01, p <0.0002). On the other hand, the risk to opiate or cannabinoid use was not increased. The birth weight (2798.1 -+ 772.6 gm vs 2581.2 +- 597.2 gm), length (47.1 _+ 7.6 cm vs 43.5 _+ 20.8 cm), and head circumference (32.6 + 2.8 cm vs 31.0 _+ 12.6 cm) were significantly (p <0.05) lower among infants with a positive drug screening result, compared with those who had a negative meconium drug screening result and specifically among infants whose results for cocaine were positive. The denial rate in maternal drug use was high. Among 449 infants with positive test results for drugs, 204 (45.5%) had mothers who denied current drug use. The incidence of positive maternal serologic results (11.4% vs 9.3%) or congenital syphilis (8.2% vs 5.9%) among the infants with positive drug screening results was high and was not significantly different (p <0.34 by Pearson chi-square analysis) whether the mother admitted to or denied drug use. DISCUSSION The relationship between maternal drug use and congenital syphilis was previously reported in two studies) 1' 12 However, drug use in both studies was determined by ma-
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291
Table II. Odds ratio and 95% confidence interval of positive meconium drug screening result to positive maternal serology result or congenital syphilis
Odds ratio (95% el)
Meconium drug screening (+) Meconium drug screening (+) Cocaine (+) Opiate (+) Cannabinoid
(+) Serology 2.5 (1.5-4.1) 2.5 (1.6-4.2) 0.9 (0.38-2.5) 0.9 (0.2-3.8)
(+) Syphilis 3.0 (1.6-5.7) 3.7 (1.9-7.0) 0.2 (0.03-2.1) 0.7 (0.1-5.2)
CI, Confidenceinterval;+, positiveresult.
temal history, urine toxicology, or both methods, which have relatively lower sensitivity for drug detection, e This study is more comprehensive for two reasons: ( 1 ) i t uses a large population of infants (N = 1012) who had drug testing for criteria other than a maternal history of current drug use, and (2) drug testing was done by a more sensitive method (i.e., meconium analysis).2 As a result of the latter, 20% more infants (N = 245) were identified as having positive results, with cocaine being the principal drug found. Noteworthy is that among the infants with positive drug test results, the incidence of positive maternal serologic results (RPR/FTAABS) or congenital syphilis was high and not significantly different among groups whether the mother admitted to or denied drug use. This implies that the risk of congenital syphilis is equally high among drug-exposed infants whose mothers denied current drug use. This study demonstrates that the relative risk of maternal or congenital syphilis is high with maternal drug use, particularly with cocaine. Noteworthy is that the selection of infants for drug testing was based on criteria that could also serve as risk factors for syphilis. Yet drug positivity remained as the most significant factor that was associated with maternal or congenital syphilis. There may be several reasons for this: (1) poor prenatal care among the pregnant drug addict, and (2) predisposing sexual behaviors in this group of mothers. 7-1° There is a high incidence of poor or inadequate prenatal care among pregnant addicts. 2 This results in a failure to identify and adequately treat these women early in pregnancy; consequently, the rate of transmission of syphilis to their infants is increased. However, among women with poor prenatal care, only cocaine use was associated with a high risk of positive serologic findings in the mother (odds ratio 4.7, 95% confidence interval 1.55 to 14.51, p <0.003) or congenital syphilis in the infant (odds ratio 5.1, 95% confidence interval 1.49 to 17.8, p <0.004). Thus some additional forms of sexual behavior in the pregnant cocaine user predispose her further to the risk of contracting syphilis. These may include prostitution, trading of sex for drugs (cocaine), and unprotected sex. 7, 10
292
Sison et aL
Other reason(s) can be advanced to explain the increased association of cocaine use with maternal and congenital syphilis; however, these explanations remain speculative. Animal and human studies have demonstrated the adverse effects of cocaine on the immunologic and cellular defense mechanisms of the body. 15-t8 Retrovirus infection of mice with LP-BM5 murine leukemia virus has shown a decrease in the number oflgA and CD4 cells in the lamina propia, and the effect was further accentuated with cocaine administration. t5 In vivo cocaine administration in mice induced a dose-related immunosuppression of natural killer cell activity t6 and suppressed the induction of interferon and interleukins by mitogens, t7 In human beings, studies of cocaineintoxicated adults have shown reduction in the total percentage of their CD4 T cells and increase in the number of natural killer cells.18 These findings suggest that cocaine may modulate the immunocompetence of the drug user and increase susceptibility to infection. There are similarities in the lifestyle of both the heroin and cocaine abusers that increase their risk of exposure to sexually transmitted diseases. 7, 10 Similarly, in mice, the highly depressive effect of morphine or cocaine on the macrophagemediated cytostatic activity and a decrease in interleukin-loL and tumor necrosis factor production have been demonstrated. 19Thus the failure in this study to demonstrate a similar increase in the risk among infants with positive opiate results for maternal or congenital syphilis may possibly be explained by the small population of infants with positive opiate results that was studied (N = 71). One possible limitation of the study is that specific criteria were used for drug testing; thus only 12.5% of the infants born during the study period were tested. Nonetheless, among the total infants born during the study period (N = 8083), only 2.6% of their mothers had a positive serologic test results for syphilis in contrast to 7.1% positive serologic test results (p <0.05) among 1012 infants who had meconium drug screening. In summary, we conclude that drug abuse in pregnancy, specifically cocaine abuse, is significantlyassociated with an increased risk for maternal and congenital syphilis. Public health measures should therefore address both problems if adequate control is to be achieved. REFERENCES
l. Chasnoff IJ. Drug use and women: establishing a standard of care. Ann N Y Acad Sci 1989;562:208-10. 2. Ostrea EM, Brady M, Ganse S, Raymundo AL, Stevens M. Drug screening of newborns by meconium analysis: a large-
The Journal of Pediatrics February 1997
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scale, prospective, epidemiologic study. Pediatrics 1992;89: 107-12. Centers for Disease Control. Primary and secondarysyphilis-United States, 1981-1990. MMWR Morb Mortal Wkly Rep 1991;40:314-23. Rolfs RT, Nakashima AK. Epidemiology of primary and secondary syphilisin the United States, 1981 through 1989.JAMA 1990;264:1432-8. Centers for Disease Control. Regional and temporal trends in the surveillance of syphilis, US, 1986-1991. MMWR Morb Mortal Wkly Rep 1991;40:29-33. Centersfor Disease Control. Surveillanceofnotifiable diseases in the United States, 1990. MMWR Morb Mortal Wkly Rep 1991;39:39-42. Rolfs RT, Goldberg M, Sharrar RG. Risk factors for syphilis: cocaineuse and prostitution.Am J PublicHealth 1990;80:853-7. Minkoff HL, McCalla S, Delke I, Stevens R, Salwen M, Feldman J. The relationship of cocaine use to syphilis mad human immunodeficiencyvires infections among inner city parturient women. Am J Obstet Gynecol 1990;163:521-6. Centers for Disease Control.Syphilis and congenitalsyphilis-United States, 1985-1988. MMWR Morb Mortal Wkly Rep 1988;37:486-9. Centers for Disease Control. Relationship of syphilis to drug use and prostitution--Connecticut and Philadelphia, Pennsylvania. MMWR Morb Mortal Wkly Rep 1988;37:755-8. Zweig Greenberg MS, Singh T, Htoo M, Schultz S. The association between congenital syphilis and cocaine/crack use in New York City: a case-control study. Am J Public Health 1991;81:1316-8. Nanda D, Feldman J, Delke I, Chintalapally S, Minkoff H. Syphilis among parturientsat an inner city hospital: association with cocaine use and implicationsfor congenital syphilisrates. N Y State J Med 1990;90:488-90. Ostrea EM, Brady MJ, Park PM, Asensio DC, Naluz A. Drug screening of meconium in infants of drug dependent mothers; an alternative to urine testing. J Pediatr 1989;115:474-7. Centers for Disease Control. Guidelinesfor the prevention and control of congenitalsyphilis.MMWR Morb Mortal Wkly Rep 1988;37:1-12. Lopez MC, Watson RR. Effect of cocaine and murine AIDS on lamina propia T and B ceils in normal mice. Life Sci 1994; 54:147-51. Francesco P, Pica F, Croce C, Favalli C, Tubaro E. Effects of acute or daily cocaine administration on cellular immune response and virus infection in mice. Nat Immun Cell Growth Regul 1990;9:397-405. Francesco P, Mafini S, Pica F, Favalli C, Tubaro E, Garacci E. In vivo cocaine administrationinfluences lymphokineproduction and hnmoral immune response. Immunol Res 1992;11: 74-9. Ruiz P, Cleary T, Nassiri M, Steele B. Human T lymphocyte subpopnlationand NK cell alterationin persons exposed to cocaine. Clin Immunol Immunopathol 1994;70:245-50. Pacifici R, Di Carlo S, Bacosi A, Zuccaro P. Macrophage functions in drugs of abuse treated mice. Int J Immunopharmacol 1993;15:711-6.
The number of women who use illicit drugs during pregnancy has increased in the last few years.l, 2 During the same period an increase in the incidence of primary and secondary syphilis was also observed among women of child-bearing age, 3-5 resulting in an increase in the incidence of congenital syphilis.6 These trends have been ascribed to drug abuse, particularly cocaine abuse. 7-10 A correlation between congenital syphilis and maternal drug use has been suggested in two retrospective studies, 11, 12 both of which determined drug use by maternal serf-report or urine toxicology. However, these methods have low sensitivity for drag detection2; consequently, a large number of drug-exposed infants may Presented in part at the Society for Pediatric Research Meeting, May 4-7, 1992, Baltimore, Maryland. Submitted for publication Feb. 13, 1996; accepted Sept. 5, 1996. Reprint requests: Enrique M. Ostrea, Jr., MD, Department of Pediatrics, Hutzel Hospital, 4707 St. Antoine, Detroit, MI 48201. Copyright © 1997 by Mosby-Year Book, Inc. 0022-3476/97/$5.00 + 0 9/21/77831
not be detected. The risk of the latter group to congenital syphilis has not been assessed. Meconium drag analysis is a new and sensitive test to detect infants who have been gestationally exposed to drugs, 2, 13 and with its use, a larger number of drug-exposed infants can be identified. This is a retrospective review of 1012 infants FFA-ABS RPR
Fluorescenttreponemal antibody, absorbed Rapidplasmin reagin
who had been previously tested for drugs by meconium drug analysis to ascertain any correlation between syphilis/positive rapid plasmin reagin serologic test results and maternal substance abuse. METHODS The meconium drug test is used in our nursery to screen infants who are suspected of having been antenatally exposed to illicit drugs, specifically to cocaine, opiate, or cannabinoid. These include infants with the following risk
289
290
Sison et al.
The Journal of Pediatrics February 1997
Table I. Association of meconium drug screening with maternal serology or congenital syphilis (+) Serology Meconium drug screening Drug screening Negative Positive Cocaine Negative Positive Opiate Negative Positive Cannabinoid Negative Positive
(+) Syphilis
No.
(%)
p*
No.
(%)
p*
25 47
(4.4) (10.5)
0.0002
14 32
(2.5) (7.1)*
0.0004
28 44
(4.6) (11.0)
0.0001
14 32
(2.3) (8.0)
0.0002
67 5
(7.1) (7.0)
0.980
45 1
(4.8) (1.4)
0.194
70 2
(7.1) (6.5)
0.884
45 l
(4.6) (3.2)
0.719
+, Positiveresult. *Pearson chi-squareanalysis(negativevs positivegroups).
factors: (1) maternal history of cocaine, opiate, or marijuana use in the current or past pregnancy, (2) maternal history of alcohol use, defined as the consumption of at least 200 ml of an alcoholic beverage, 3 to 4 times per week, (3) poor maternal prenatal care defined as <2 prenatal visits for the entire pregnancy, (4) signs of drug withdrawal in the infant with negative maternal drug history, (5) abruptio placentae or positive result of human immunodeficiency virus screening in the mother, and (5) social risk factors, such as infant for adoption, home delivery, or teenage pregnancy. All parturients in our hospital are also routinely screened for syphilis by the RPR test, and if results are positive, are tested further by the fluorescent, treponemal, antibody absorption test. Infants who had a meconium drug test done during a select 10-month period were enrolled in the study. The medical records of the infant and mother were reviewed to determine the results of the meconium drag test, the reason(s) for drug testing, the results of the maternal serologic test for syphilis, and to verify the diagnosis of congenital syphilis on the basis of the Centers for DiseaseControl and Prevention definitions.14 Pertinent demographic and clinical data on mother and infant were obtained from the chart. No parental consent was obtained for the chart review; however, the confidentiality of the information derived from the chart review was strictly maintained. Data analysis included Pearson chi-square analysis and odds ratio for cross-tabulated data, Student t test for comparison of means, and stepwise, logistic regression to predict a dichotomous outcome variable from two or more other predictor variables. A value o f p <0.05 was used as the level of statistical significance.
RESULTS During the 10-month study period, 1012 infants who had drug testing were enrolled (52% girls, 48% boys). The mean
(SD) gestational age was 37.6-+ 3.2 weeks, length 45.5 + 15.1 cm, birth weight 2701.9 -+ 708.2 gm, and head circumference 31.9 + 8.7 cm. For the mothers, 82% were single, 85% were black women, 12.1% were white women, and 28.9% admitted to opiate or cocaine use during the present pregnancy. Based on the reasons for drug testing, 363 (35.9%) infants had a meconium drug test because of maternal history of current use of cocaine or opiate, 43 (4.2%) because of maternal illicit drug use only in the past, 133 (13.1%) because of maternal alcohol use or marijuana use, 263 (26%) because of poor maternal, prenatal care, 84 (8.3%) because of signs of withdrawal in the infant, abruptio placentae, or human immunodeficiency virus infection in the mother, and 76 (7.5%) because of social risk factors. In 50 (5%) infants, the reason for drug testing was not specified in the chart. In many instances, this may be because of a high-risk condition in the mother (e.g, single mother with multiple partners or history of other sexually transmitted diseases such as herpes simplex or hepatitis B). The results of the drugs test on 1012 infants were as follows: 449 (44.3%) were positive for any drug, 401 (39.6%) were positive for cocaine, 71 (7%) positive for opiate, and 31 (3.1%) positive for cannabinoid. The drug positivity rate was highest (83%) among infants whose mothers were current users of drugs (cocaine or opiate). However, 47% of infants whose mothers admitted only to drug use in the past or 27% of infants whose mothers admitted only to alcohol or marijuana use also had positive screening results for cocaine or opiate. Among the mothers with poor prenatal care (N = 263), 15.2% had positive results for cocaine, 1.9% had positive results for opiate, and 1.5% had positive results for cannabinoids. Seventy-two mothers (7.1%) had a positive serologic re-
The Journal of Pediatrics Volume 130, Number 2
sult (RPR/FTA-ABS), and congenital syphilis was diagnosed in 46 infants (4.5%), primarily as a result of inadequate maternal treatment. However, two infants had clinical signs of congenital syphilis (e.g., hepatosplenomegaly and/or long bone metaphyseal radiolucencies). The association of the meconium drug screen results with maternal RPR/FTA-ABS results and congenital syphilis is shown in Tables I and II, respectively. The incidence and relative risk of a positive serology result or congenital syphilis were significantly high among infants with a positive meconium drug screen result or those whose results were positive for cocaine. However, forward, stepwise logistic regression of the following variables--cocaine, meconium drug screen, opiate, and cannabinoid--showed that only the positive cocaine test result was significantly (p <0.001) predictive of a positive serologic result or congenital syphilis. When controlling for alcohol use, a positive drug screen result for cocaine was still significantly associated with a positive serologic result (11% vs 4.7%, p <0.001 by Pearson chi-square; odds ratio = 2.5, confidence interval 1.5 to 4.2) or congenital syphilis (8.0% vs 2.2%, p <0.0001 by Pearson chi-square, odds ratio = 3.9, confidence interval 1.9 to 7.9). Among mothers who had a positive serology resuk for syphilis, the risk of cocaine use was significantly increased (odds ratio of 2.56, 95% confidence interval 1.57 to 4.19, p <0.0001). Similarly, among infants in whom congenital syphilis was diagnosed, the risk of cocaine use in their mothers was also increased (odds ratio 3.69, 95% confidence interval 1.94 to 7.01, p <0.0002). On the other hand, the risk to opiate or cannabinoid use was not increased. The birth weight (2798.1 -+ 772.6 gm vs 2581.2 +- 597.2 gm), length (47.1 _+ 7.6 cm vs 43.5 _+ 20.8 cm), and head circumference (32.6 + 2.8 cm vs 31.0 _+ 12.6 cm) were significantly (p <0.05) lower among infants with a positive drug screening result, compared with those who had a negative meconium drug screening result and specifically among infants whose results for cocaine were positive. The denial rate in maternal drug use was high. Among 449 infants with positive test results for drugs, 204 (45.5%) had mothers who denied current drug use. The incidence of positive maternal serologic results (11.4% vs 9.3%) or congenital syphilis (8.2% vs 5.9%) among the infants with positive drug screening results was high and was not significantly different (p <0.34 by Pearson chi-square analysis) whether the mother admitted to or denied drug use. DISCUSSION The relationship between maternal drug use and congenital syphilis was previously reported in two studies) 1' 12 However, drug use in both studies was determined by ma-
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291
Table II. Odds ratio and 95% confidence interval of positive meconium drug screening result to positive maternal serology result or congenital syphilis
Odds ratio (95% el)
Meconium drug screening (+) Meconium drug screening (+) Cocaine (+) Opiate (+) Cannabinoid
(+) Serology 2.5 (1.5-4.1) 2.5 (1.6-4.2) 0.9 (0.38-2.5) 0.9 (0.2-3.8)
(+) Syphilis 3.0 (1.6-5.7) 3.7 (1.9-7.0) 0.2 (0.03-2.1) 0.7 (0.1-5.2)
CI, Confidenceinterval;+, positiveresult.
temal history, urine toxicology, or both methods, which have relatively lower sensitivity for drug detection, e This study is more comprehensive for two reasons: ( 1 ) i t uses a large population of infants (N = 1012) who had drug testing for criteria other than a maternal history of current drug use, and (2) drug testing was done by a more sensitive method (i.e., meconium analysis).2 As a result of the latter, 20% more infants (N = 245) were identified as having positive results, with cocaine being the principal drug found. Noteworthy is that among the infants with positive drug test results, the incidence of positive maternal serologic results (RPR/FTAABS) or congenital syphilis was high and not significantly different among groups whether the mother admitted to or denied drug use. This implies that the risk of congenital syphilis is equally high among drug-exposed infants whose mothers denied current drug use. This study demonstrates that the relative risk of maternal or congenital syphilis is high with maternal drug use, particularly with cocaine. Noteworthy is that the selection of infants for drug testing was based on criteria that could also serve as risk factors for syphilis. Yet drug positivity remained as the most significant factor that was associated with maternal or congenital syphilis. There may be several reasons for this: (1) poor prenatal care among the pregnant drug addict, and (2) predisposing sexual behaviors in this group of mothers. 7-1° There is a high incidence of poor or inadequate prenatal care among pregnant addicts. 2 This results in a failure to identify and adequately treat these women early in pregnancy; consequently, the rate of transmission of syphilis to their infants is increased. However, among women with poor prenatal care, only cocaine use was associated with a high risk of positive serologic findings in the mother (odds ratio 4.7, 95% confidence interval 1.55 to 14.51, p <0.003) or congenital syphilis in the infant (odds ratio 5.1, 95% confidence interval 1.49 to 17.8, p <0.004). Thus some additional forms of sexual behavior in the pregnant cocaine user predispose her further to the risk of contracting syphilis. These may include prostitution, trading of sex for drugs (cocaine), and unprotected sex. 7, 10
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Other reason(s) can be advanced to explain the increased association of cocaine use with maternal and congenital syphilis; however, these explanations remain speculative. Animal and human studies have demonstrated the adverse effects of cocaine on the immunologic and cellular defense mechanisms of the body. 15-t8 Retrovirus infection of mice with LP-BM5 murine leukemia virus has shown a decrease in the number oflgA and CD4 cells in the lamina propia, and the effect was further accentuated with cocaine administration. t5 In vivo cocaine administration in mice induced a dose-related immunosuppression of natural killer cell activity t6 and suppressed the induction of interferon and interleukins by mitogens, t7 In human beings, studies of cocaineintoxicated adults have shown reduction in the total percentage of their CD4 T cells and increase in the number of natural killer cells.18 These findings suggest that cocaine may modulate the immunocompetence of the drug user and increase susceptibility to infection. There are similarities in the lifestyle of both the heroin and cocaine abusers that increase their risk of exposure to sexually transmitted diseases. 7, 10 Similarly, in mice, the highly depressive effect of morphine or cocaine on the macrophagemediated cytostatic activity and a decrease in interleukin-loL and tumor necrosis factor production have been demonstrated. 19Thus the failure in this study to demonstrate a similar increase in the risk among infants with positive opiate results for maternal or congenital syphilis may possibly be explained by the small population of infants with positive opiate results that was studied (N = 71). One possible limitation of the study is that specific criteria were used for drug testing; thus only 12.5% of the infants born during the study period were tested. Nonetheless, among the total infants born during the study period (N = 8083), only 2.6% of their mothers had a positive serologic test results for syphilis in contrast to 7.1% positive serologic test results (p <0.05) among 1012 infants who had meconium drug screening. In summary, we conclude that drug abuse in pregnancy, specifically cocaine abuse, is significantlyassociated with an increased risk for maternal and congenital syphilis. Public health measures should therefore address both problems if adequate control is to be achieved. REFERENCES
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