- Email: [email protected]
Adverse perinatal outcome in parturients who use crack cocaine
Adverse Perinatal Outcome in Parturients Who Use Crack Cocaine MARGARET E. SPRAUVE, MD, MPH, MICHAEL K. LINDSAY, MD, MPH, SARAH HERBERT, MD, AND WILLIAM GRAVES, PhD Objective: To determine the risk of adverse pregnancy out• come among crack cocaine users in a large homogeneous prenatal population with objective documentation of drug use. Methods: A retrospective cohort study was performed on a population of inner-city women who were offered routine voluntary urine drug screening and who delivered between January and December 1992 at a large county hospital. The study population consisted of 483 users (positive drug screens) and 3158 non-users (negative drug screens). Univar• iate analysis and multiple logistic regression were used to identify the relation between crack cocaine use and adverse perinatal outcome. Results: Users were significantly more likely than non• users to deliver low birth weight (LBW) infants (31.3% versus 14.9%; crude odds ratio [ORl 2.6; 95% confidence interval [CI] 2.1,3.2), growth-restricted infants (29.0% versus 13.0%; crude OR 2.7; 95% CI 2.2, 3.4), and preterm infants (28.2% versus 17.1%; crude OR 1.9; 95% CI 1.5, 2.4). In addition, users were more likely to have abruptions (3.3% versus 1.1%; crude OR 3.0; 95% CI 1.6, 5.6) and infants with low 5-minute Apgar scores (7.9% versus 4.5%; crude OR 1.8; 95% CI 1.2, 2.7). After adjusting for confounders (including alcohol use and smoking), only the risks of LBW and fetal growth restriction (FGR) remained significant, with adjusted OR 1.6 (95% CI 1.03, 2.4) and adjusted OR 1.7 (95% CI 1.2, 2.3), respectively. Although there was no significant differ• ence in the rate of low 5-minute Apgar scores between users and non-users after controlling for confounders, users with a positive urine drug screen within 1 week of delivery were significantly more likely than non-users to deliver infants with low 5-minute Apgar scores: crude OR 2.4; adjusted OR 2.0 (95% CI 1.1, 3.7). Conclusion: In this inner-city population, crack cocaine use is associated with adverse pregnancy outcomes, as noted by increased risks of LBW and FGR. (Obstet Gynecol 1997; 89:674-8. © 1997 by The American College of Obstetricians and Gynecologists.)
From the Department of Gynecology and Obstetrics, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, Georgia.
674 0029-7844/97/$17.00
PH 50029-7844(97)00078-1
Cocaine is a central nervous system stimulant that blocks neuronal uptake of norepinephrine, thus increas• ing heart rate and blood pressure. Because of its low molecular weight and high water solubility, cocaine readily crosses the placenta. 1 The relatively low pH of fetal blood and the low fetal level of plasma esterases that metabolize the drug may facilitate the accumula• tion of cocaine in the fetus. Cocaine can be put in an alkaline solution and extracted to yield the water• insoluble, heat-stable crack cocaine. Crack cocaine use accelerated in the early 1990s in women of reproductive age because of its ease of use, rapid intense "high," and relatively low cost.2 The impact of cocaine on human reproduction and perinatal outcome received widespread interest in the late 1980s. Evidence of a dramatic increase in the antenatal use of cocaine focused attention on its adverse consequences for fetal development. Commonly re• ported adverse perinatal outcomes of antenatal cocaine use include increased risk of low birth weight (LBW), premature delivery, fetal growth restriction (FGR), and abruptio placentae? Maternal cocaine use adds an esti• mated $8766 to $11,925 to neonatal hospitalization costs compared with those of neonates born to drug-free women. 3,4 The most frequently studied population of pregnant cocaine users has been urban minority women of low socioeconomic status, who have an increased risk for poor pregnancy outcome even in the absence of cocaine use.5-11 Many of these studies included relatively small numbers of women,5-7 did not have objective criteria for assessing cocaine use,8,9 or did not control for multiple covariates.5-7,tD,11 Therefore, these studies failed to identify possible confounding factors. In addition, none of these studies distinguished between crack cocaine and other methods of cocaine use. There is evidence that crack cocaine generates unique metabolic prod• ucts 12 and may influence the maternal-fetal environ• ment differently than other methods of cocaine use. A
Obstetrics & Gynecology
1991 survey of parturients at our institution who re• ceived a urine toxicology screen revealed that greater than 85% of self-reported cocaine users smoked crack cocaine exclusivelyY The purpose of this study was to examine the effect of antenatal crack cocaine use on several perinatal out• comes in a large homogeneous population with routine documentation of urine drug screen(s), using multivar• iate analysis to adjust for potential confounders.
Materials and Methods Grady Memorial Hospital, located in Atlanta, Georgia, which serves a predominantly indigent population, began a policy of routine voluntary prenatal urine drug screening in 1990. Patients are tested for cocaine and other drugs at their initial visit and peripartum (within a week of delivery). Patients who are seen in the labor and delivery unit for extended monitoring (greater than 2 hours) or are admitted to the antepartum floor for any reason during pregnancy are also tested at that time. Patients with positive prenatal screens receive serial screening at each prenatal visit and are referred to the Psychiatric Obstetrics Clinic for counseling regarding drug use and the potential harmful maternal and fetal effects. Patients are also offered emollment in either an inpatient or outpatient drug rehabilitation program. Patients with no prenatal care at the time of delivery undergo drug screening and are interviewed peripar• tum. The results of the urine assay are available only to the medical staff and are not reported to outside author• ities. No woman is denied medical services if she refuses a urine assay. Data are entered on the obstetric discharge summary and subsequently into a computer• ized data base. Urine samples were tested for the presence of the cocaine metabolite benzoylecgonine. An enzyme• multiplied immunoassay technique was performed us• ing an automated chemistry analyzer. This analyzer is calibrated such that any sample containing at least 300 ng/mL of benzoylecgonine-the federally defined stan• dard cutoff for initial drug screening assays-gives a positive result. This assay is predicted to become neg• ative within 5 days after the use of street doses of cocaine. 14 This study was conducted on pregnant women who initiated care, received urine drug screens, and delivered between January 1, 1992 and December 31, 1992. To avoid misdassification, we excluded from the study patients who initiated care in 1991 but deliv• ered in 1992 and patients who initiated care in 1992 but delivered in 1993. Patient groups were developed based on urine drug screen results. The study group included any patient with a positive urine drug screen during pregnancy or within a week of delivery (n = 483). The
VOL. 89, NO.5, PART 1, MAY 1997
control group included all other patients delivering in 1992 with negative urine drug screen(s) (n = 3158). Information from the obstetric forms was available for all patients. In addition to information about ante• natal cocaine use, the following variables were ex• tracted: maternal age, parity, race, percent of ideal body weight, marital status, education, alcohol use, tobacco use, and hypertensive disorders. Clinical and demo• graphic data were compared between the groups. Dif• ferences in proportions were assessed using 1" analysis, and differences in means were assessed using the two• tailed t test. Univariate analysis was used to compare various perinatal outcomes between the user and non-user groups. Outcomes included LBW, FGR, preterm deliv• ery, abruptio placentae, low 5-minute Apgar scores, perinatal mortality, congenital malformations, and ce• sarean delivery rate. Finally, multiple logistic regression was used to control for potentially confounding vari• ables. Additional multivariate analysis was performed to compare the rates of abruptio placentae and low 5-minute Apgar scores in users with acute intoxication (positive urine drug screen within a week of delivery) versus non-users. For the purposes of this study, we used the following definitions. Prenatal care was defined as three or more prenatal visits, alcohol abuse as maternal consumption of four drinks per week, LBW as 2500 g or less, FGR as weight at the tenth percentile or less for gestational age, and preterm delivery as 36 weeks' gestation or less. The diagnosis of abruptio placentae was based on clinical recognition of vaginal bleeding, abdominal pain, con• sumptive coagulopathy, positive Kleihauer-Betke stain, or retroplacental clot. Gestational age was assigned using last menstrual period in conjunction with physi• cal and ultrasound examinations.
Results Of the women who were eligible, 86.5% consented to urine drug screens. White parturients were significantly more likely to decline testing 00.0% versus 5.8%) than black or "other" parturients. The prevalence of crack cocaine use during pregnancy in 1992 in our popula• tion, detected by urine cocaine screens, was 13.3%. Maternal demographic and prenatal data for users and non-users are summarized in Table 1. The group of crack cocaine users tended to be older, single, black (Figure 1), multiparous women. Crack cocaine users were significantly more likely than controls to abuse alcohol (23.6% versus 3.0%), to use tobacco (75.0% versus 16.2%), to weigh less than 100% of ideal body weight (35.6% versus 24.8%), and to receive inadequate prenatal care (58.0% versus 23.3%),
Sprauve et al
Crack Cocaine Use in Pregnancy
675
Table 2. Univariate Analysis of Selected Prenatal Outcomes in Users Versus Non-Users
Table 1. Selected Demographic Characteristics of Users Versus Non-Users Users 483)
Characteristic
(n =
Age (y) <18 18-34 >34 Marital status* Single Married Other Parity
o
1 2:2 Education* <12th 2:12th Prenatal care Adequate Inadequate Alcohol abuse Yes No Tobacco use" Yes No Ideal birth weight <100 percentile 2:100 percentile
Non-users 3158)
4(0.8%) 439 (90.9%) 40 (8.3%)
468 (14.8%) 2519 (79.8%) 171 (5.4%)
<.01
397 (82.2%) 37(7.7%) 49 (10.1%)
2211 (70.1%) 693 (22.0%) 252 (8.0%)
<.01
61 (12.6%) 96 (19.9%) 326(67.5%)
1163 (36.8%) 859 (27.2%) 1136 (36.0%)
<.01
118(25.9%) 338 (74.1%)
822(26.7%) 2258 (73.3%)
.61
203 (42.0%) 280(58.0%)
2421 (76.7%) 737(23.3%)
<.01
114 (23.6%) 369(76.4%)
94 (3.0%) 3064 (97.0%)
<.01
315 (75.0%) 105 (25.0%)
444 (16.2%) 2299 (83.8%)
<.01
141 (35.6%) 255 (64.4%)
733 (24.8%) 2222 (75.2%)
<.01
P < .01. There was no difference between the groups in the prevalence of hypertension 0.1% versus 1.2%). Table 2 summarizes the univariate analysis of obstet• ric and perinatal outcomes in users versus non-users. Crack cocaine users were significantly more likely than
:;:-:-;:2--------------1
100...--..
ClI
Non-users
Crude OR (95% CI)
Low birth weight Fetal growth reslriction Premature delivery Abruptio placentae Low 5-min Apgar score Fetal death Neonatal death Congenital malformations Cesarean delivery
31.3% 29.0% 28.2% 3.3% 7.9% 1.5% 1.0% 2.3% 18.0%
14.9% 13.0% 17.1% 1.1% 4.5% 1.4% 0.8% 3.6% 15.3%
2.59 (2.07, 3.23)* 2.74 (2.18, 3.44)" 1.90 (1.52, 2.38)* 2.97 (1.57, 5.58)* 1.82 (1.23, 2.67)* 1.07 (0.44, 2.49) 1.37 (0.46, 3.79) 0.62 (0.31, 1.19) 1.22 (0.94, 1.58)
OR
=
odds ratio; CI = confidence interval.
non-users to deliver LBW (OR 2.59; 95% CI 2.07, 3.23), growth restricted (OR 2.74; 95% CI 2.18, 3.44), and preterm infants (OR 1.90; 95% CI 1.52, 2.38). In addition, cocaine users were significantly more likely to have an abruption (OR 2.97; 95% CI 1.57, 5.58) and to deliver an infant with a 5-minute Apgar score less than 7 (OR 1.82; 95% CI 1.23, 2.67). No differences were found between the groups in the incidence of fetal death, neonatal death, congenital malformation, or cesarean delivery. To ensure that the increased risks of LBW, FGR, preterm delivery, abruptio placentae, and low 5-minute Apgar score among users were not attributable to confounding variables, we performed multiple logistic regression to adjust for potential confounders (Table 3). Antenatal crack cocaine use remained independently associated with delivery of LBW (adjusted OR 1.59; 95% CI 1.03, 2.43) and growth-restricted infants (adjusted OR 1.70; 95% CI 1.24, 2.32). However, the risks of preterm delivery (adjusted OR 0.88; 95% CI 0.63, 1.22), abruptio placentae (adjusted OR 1.41; 95% CI 0.64, 3.10), and low 5-minute Apgar score (adjusted OR 1.38; 95% Table 3. Adjusted Odds Ratios and Confidence Intervals for Selected Perinatal Outcomes in Users Versus Non-Users
71111
80
Variable
Crude OR
Adjusted OR (950/0 cn
40
Low birth weightt Fetal growth reslriction* Premature delivery§ Abruptio placentaell Low 5-min Apgar score'
2.59 2.74 1.90 2.97 1.82
1.59 (1.03,2.43)* 1.70 (1.24, 2.32)* 0.88 (0.63, 1.22) 1.41 (0.64,3.10) 1.38 (0.57, 2.30)
i
0
~
Users
* p < .05.
" Because some records had incomplete information, the number of cases in some categories varies.
80
Outcome
p
(n =
20
153
02
0
Figure 1. Racial breakdown of parturients who use crack cocaine and non-using parturients. The majority of parturients in the "other" category are Hispanic and Asian.
676 Sprauve et al
Crack Cocaine Use in Pregnancy
OR = odds ratio; CI = confidence interval. * p < .05. Independent covariates for each model are listed: t Alcohol, tobacco, <1000/0 ideal body weight, prenatal care, preterm delivery, age. *Alcohol, tobacco, <100% ideal body weight, hypertension, marital status. § Tobacco, <100% ideal body weight, hypertension, abruption, pre• natal care, age. I Tobacco, hypertension. 'i Hypertension, FGR, abruption.
Obstetrics & Gynecology
CI 0.57, 2.30) among crack cocaine users did not persist (Table 3). To evaluate the effects of acute crack cocaine use on intrapartum events, we compared the rate of abruption and low 5-minute Apgar score between users with a positive urine drug screen within a week of delivery and non-users. After controlling for hypertension and tobacco use, we found no difference between the groups in the rate of abruption (crude OR 3.34; adjusted OR 1.37; 95% CI 0.57, 3.30). However, after controlling for hypertension, FGR, and abruption, users with recent crack cocaine use were significantly more likely to deliver a neonate with a low 5-minute Apgar score than were non-users (crude OR 2.35; adjusted OR 2.04; 95% CI 1.13, 3.68).
Discussion Because many of the adverse perinatal outcomes asso• ciated with cocaine use can potentially be attributable to confounding factors, it is imperative that these variables be adjusted for in observational studies addressing this issue. After controlling for relevant covariates, we were able to show, in a large homogeneous prenatal popula• tion, an independent association between antenatal crack cocaine use and both LBW and FGR. These results are consistent with findings in several other stud• ies.8.10.15.16 On the other hand, Mastrogiannis et al 6 examined the relation between antenatal cocaine use and growth-retarded infants and found no association. However, that study included only 40 patients in the cocaine group and thus, their results may be attribut• able to a type II error. Cocaine has vasoconstrictive effects on the maternal uteroplacental vasculature, which reduce uterine blood flow and restrict nutrient delivery to the fetus. 17- 19 This is the mechanism postu• lated to cause diminished birth weight and FGR. A meta-analysis of 26 studies performed from 1987 to 1991 revealed an association between cocaine use and premature delivery, abruptio placentae, and low 5-minute Apgar score. 2 However, methodologic differ• ences among these studies weaken their comparability, and few of the studies controlled for potential con• founders. In addition, none of these studies distin• guished between different methods of cocaine use. In contrast to previous studies, ours controlled for poten• tial confounders including tobacco use, hypertension, and prenatal care, and we were unable to show an association between crack cocaine use and preterm delivery, abruption, or low 5-minute Apgar score. Our failure to find an association between abruption and crack cocaine use requires further exploration. Abruptio placentae is frequently reported as a compli• cation of antenatal cocaine use,2°·21 Placental pathologic
VOL. 89, NO.5, PART 1, MAY 1997
findings such as decidual vascular thickening, villous ischemic infarction, and intervillous hemorrhage have been reported and implicated as the cause of the in• creased incidence of abruption found in cocaine users. 20 After controlling for tobacco use, we did not find an independent association between abruption and ante• natal crack cocaine use. Our results are similar to those in several smaller studies that failed to find an associ• ation between cocaine use and abruption. 6.1o A possible explanation for this finding is that the clinically evident increased rate of abruption observed in cocaine-using parturients is due to acute cocaine intoxication or to concomitant tobacco use. To pursue this hypothesis more fully, we examined the rate of abruption in users with acute crack cocaine use (positive urine drug screen within a week of delivery) versus non-users, and were still unable to detect a significant difference between the groups. However, parturients with acute crack cocaine use were significantly more likely than non-users to deliver neonates with low 5-minute Apgar scores. In our analysis, abruption was independently associated with low 5-minute Apgar score. Thus, our inability to find an increase in the rate of abruption may be due to lack of recognition of subclinical placental abruption or to under-reporting of abruption at the time of delivery. Our study has several strengths. As a result of our policy of routine urine drug screening on pregnant patients at Grady Memorial Hospital, we had the op• portunity to capture a large sample of predominantly crack cocaine-using parturients. Ascertainment bias was minimized because approximately 87% of the preg• nant women who were eligible consented to urine drug screens, and misclassification was reduced because women were categorized by objective criteria and not patient recall. In addition, we were able to control for potential confounders in our analysis. It is important to acknowledge that our study has several limitations. First, some patients who tested negative on their initial screen had no additional testing until delivery. If these patients were screened through• out pregnancy, some of them may have tested positive. Unless they tested positive at delivery, these patients would be included in the control group, biasing the results toward the null hypothesis. Second, no attempt was made to quantify the amount, the frequency, or the pattern of cocaine use. In addition, cocaine users have a marked tendency to abuse more than one substance. 22 Unfortunately, we did not have sufficient data on other illicit drug use to include it in our analysis. The avail• able data on alcohol and tobacco use did not include quantity and pattern of use, increasing the possibility of a beta error. We were missing data on tobacco use in 13% of the patients; however, the missing data were distributed proportionately between the groups, and
Sprauve et al
Crack Cocaine Use in Pregnancy
677
these patients had similar demographic characteristics as those patients for whom data on tobacco use were available. Finally, although this study was performed on a largely homogeneous population, the lifestyle of the addicted pregnant woman is probably not compa• rable to that of non-drug users or occasional drug users. As addiction worsens, the need for more frequent use overwhelms all other considerations and may lead to behavioral patterns that jeopardize maternal and fetal well-being in a manner for which we may not be able to adjust. lO Future studies should assess the impact of antenatal intervention on improving outcome in this high-risk population. A recent retrospective cohort study using birth certificate data in New York City suggested that prenatal care among cocaine users decreased the risk of LBW in this population. 23 In our study, approximately 50% of cocaine users received minimal or no prenatal care. Inadequate or lack of prenatal care was an inde• pendent predictor of LBW. The potentially beneficial effects of prenatal care on adverse perinatal outcomes in cocaine-using parturients have yet to be characterized adequately. The greatest difficulty encountered in studying the effects of prenatal care on perinatal out• come is defining "adequate" prenatal care. Our institu• tion uses a comprehensive prenatal care plan for women identified as crack cocaine users. It employs a team experienced in psychosocial behavior, drug reha• bilitation, social services, community health, and nutri• tion. Whether this approach leads to improved perina• tal outcome is unknown. Given the estimated $500 million to $6.12 billion per year spent on caring for neonates exposed to cocaine during pregnancy, it is imperative to investigate the effectiveness of our current model of prenatal care as well as other intervention strategies, such as increased antepartum surveillance and outpatient peer counseling programs.
References 1. Roe DA, Little BB, Bawdon RE, Gilstrap LC. Metabolism of cocaine by human placentas: Implications for fetal exposure. Am J Obstet Gynecol 1990;163:715-8. 2. Glantz JC, Woods JR. Cocaine, heroin, and phencyclidine: Obstet• ric perspectives. Clin Obstet Gynecol 1993;36:279-95. 3. Calhoun Be, Watson PT. The cost of maternal cocaine abuse: I. Perinatal cost. Obstet GynecoI1991;78:731-4. 4. Phibbs C5, Bakman DA, Schwartz RM. The neonatal costs of maternal cocaine use. JAMA 1991;266:1521-6. 5. Chasnoff Il, Griffin DR, MacGregor S, Dirkes K, Bums KA. Tem• poral patterns of cocaine use in pregnancy. JAMA 1989;261:1741-4. 6. Mastrogiannis OS, Decavalas GO, Verma V, Tejani N. Perinatal outcome after recent cocaine usage. Obstet GynecoI1990;76:8-11.
678 Sprauve et al
Crack Cocaine Use in Pregnancy
7. Chasnoff IJ, Burns WJ, Schnoll 5H, Burns KA. Cocaine use in pregnancy. N Engl J Med 1985;313:666-9. 8. Cherukuri R Minkoff H, Feldman J, Parekh A, Glass L. A cohort study of alkaloidal cocaine ("crack") in pregnancy. Obstet Gynecol 1988;72:147-51. 9. Handler A, Kistin N, Davis F, Ferre C. Cocaine use during pregnancy: Perinatal outcomes. Am J EpidemioI1991;133:818-25. 10. MacGregor 5N, Keith LG, Chasnoff IJ, Rosner MA, Chisum GM, Shaw P, et a!. Cocaine use during pregnancy: Adverse perinatal outcome. Am J Obstet Gynecol 1987;157:686-90. 11. Ryan L, Ehrlich 5, Finnegan L. Cocaine abuse in pregnancy: Effects on the fetus and newborn. Neurotoxicol TeratoI1987;9:295-9. 12. el-Fawal HA, Woods RW. Airway smooth muscle relaxant effects of the cocaine pyrolysis product, methylecgonidine. J Pharmacol Exp Ther 1995;272:991-6. 13. Lindsay MK, CarmichaelS, Peterson H, Risby J, Williams H, Klein L. The correlation between self-report of cocaine use and urine toxicology in an inner-city prenatal population. J Natl Med Assoc 1997;89:57-60. 14. Ambre J. The unnary excretion of cocaine and metabolites in humans: A kinetic analysis of published data. J Anal Toxicol 1985;9:241-4. 15. Bates CK. Medical risks of cocaine use. West J Med 1988;148:440-4. 16. Handler A, Kistin N, Davis F, Ferre C. Cocaine use during pregnancy: Perinatal outcomes. Am J EpidemioI1991;133:818-25. 17. Sherman WT, Gautien RF. Effects of certain drugs on perfused human placenta. Norepinephrine release by bradykinin. J Pharm Sci 1972;61:878-83. 18. Woods JR, Plessinger MA, Clark KE. Effect of cocaine on uterine blood fetal oxygenation. JAMA 1987;257:957-62. 19. Moore TR, Song J, Miller L, Key Te, Resnik R. Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus. Am J Obstet Gynecol 1986;155:883-8. 20. Acher D, Sachs BP, Tracey KJ, Wise WE. Abruptio placentae associated with cocaine use. Am J Obstet GynecoI1983;146:220-1. 21. Townsend RR, Laing Fe, Brooke J. Placental abruption associated with cocaine use. AJR Am J Roentgenol 1988;150:1339-40. 22. Chasnoff IJ. Cocaine and pregnancy: Clinical and methodologic issues. Clin Perinatol 1991;18:113-23. 23. Racine A, Joyce T, Anderson R. The association between prenatal care and birth weight among women exposed to cocaine in New York City. JAMA 1993;270:1581-6.
Address reprint requests to:
Margaret E. Sprauve, MD, MPH Department of Gynecology and Obstetrics Emory University School of Medicine 69 Butler Street, SE Atlanta, GA 30303
Received October 21, 1996. Received in revised form January 10, 1997. Accepted January 21, 1997. Copyright © 1997 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology
From the Department of Gynecology and Obstetrics, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, Georgia.
674 0029-7844/97/$17.00
PH 50029-7844(97)00078-1
Cocaine is a central nervous system stimulant that blocks neuronal uptake of norepinephrine, thus increas• ing heart rate and blood pressure. Because of its low molecular weight and high water solubility, cocaine readily crosses the placenta. 1 The relatively low pH of fetal blood and the low fetal level of plasma esterases that metabolize the drug may facilitate the accumula• tion of cocaine in the fetus. Cocaine can be put in an alkaline solution and extracted to yield the water• insoluble, heat-stable crack cocaine. Crack cocaine use accelerated in the early 1990s in women of reproductive age because of its ease of use, rapid intense "high," and relatively low cost.2 The impact of cocaine on human reproduction and perinatal outcome received widespread interest in the late 1980s. Evidence of a dramatic increase in the antenatal use of cocaine focused attention on its adverse consequences for fetal development. Commonly re• ported adverse perinatal outcomes of antenatal cocaine use include increased risk of low birth weight (LBW), premature delivery, fetal growth restriction (FGR), and abruptio placentae? Maternal cocaine use adds an esti• mated $8766 to $11,925 to neonatal hospitalization costs compared with those of neonates born to drug-free women. 3,4 The most frequently studied population of pregnant cocaine users has been urban minority women of low socioeconomic status, who have an increased risk for poor pregnancy outcome even in the absence of cocaine use.5-11 Many of these studies included relatively small numbers of women,5-7 did not have objective criteria for assessing cocaine use,8,9 or did not control for multiple covariates.5-7,tD,11 Therefore, these studies failed to identify possible confounding factors. In addition, none of these studies distinguished between crack cocaine and other methods of cocaine use. There is evidence that crack cocaine generates unique metabolic prod• ucts 12 and may influence the maternal-fetal environ• ment differently than other methods of cocaine use. A
Obstetrics & Gynecology
1991 survey of parturients at our institution who re• ceived a urine toxicology screen revealed that greater than 85% of self-reported cocaine users smoked crack cocaine exclusivelyY The purpose of this study was to examine the effect of antenatal crack cocaine use on several perinatal out• comes in a large homogeneous population with routine documentation of urine drug screen(s), using multivar• iate analysis to adjust for potential confounders.
Materials and Methods Grady Memorial Hospital, located in Atlanta, Georgia, which serves a predominantly indigent population, began a policy of routine voluntary prenatal urine drug screening in 1990. Patients are tested for cocaine and other drugs at their initial visit and peripartum (within a week of delivery). Patients who are seen in the labor and delivery unit for extended monitoring (greater than 2 hours) or are admitted to the antepartum floor for any reason during pregnancy are also tested at that time. Patients with positive prenatal screens receive serial screening at each prenatal visit and are referred to the Psychiatric Obstetrics Clinic for counseling regarding drug use and the potential harmful maternal and fetal effects. Patients are also offered emollment in either an inpatient or outpatient drug rehabilitation program. Patients with no prenatal care at the time of delivery undergo drug screening and are interviewed peripar• tum. The results of the urine assay are available only to the medical staff and are not reported to outside author• ities. No woman is denied medical services if she refuses a urine assay. Data are entered on the obstetric discharge summary and subsequently into a computer• ized data base. Urine samples were tested for the presence of the cocaine metabolite benzoylecgonine. An enzyme• multiplied immunoassay technique was performed us• ing an automated chemistry analyzer. This analyzer is calibrated such that any sample containing at least 300 ng/mL of benzoylecgonine-the federally defined stan• dard cutoff for initial drug screening assays-gives a positive result. This assay is predicted to become neg• ative within 5 days after the use of street doses of cocaine. 14 This study was conducted on pregnant women who initiated care, received urine drug screens, and delivered between January 1, 1992 and December 31, 1992. To avoid misdassification, we excluded from the study patients who initiated care in 1991 but deliv• ered in 1992 and patients who initiated care in 1992 but delivered in 1993. Patient groups were developed based on urine drug screen results. The study group included any patient with a positive urine drug screen during pregnancy or within a week of delivery (n = 483). The
VOL. 89, NO.5, PART 1, MAY 1997
control group included all other patients delivering in 1992 with negative urine drug screen(s) (n = 3158). Information from the obstetric forms was available for all patients. In addition to information about ante• natal cocaine use, the following variables were ex• tracted: maternal age, parity, race, percent of ideal body weight, marital status, education, alcohol use, tobacco use, and hypertensive disorders. Clinical and demo• graphic data were compared between the groups. Dif• ferences in proportions were assessed using 1" analysis, and differences in means were assessed using the two• tailed t test. Univariate analysis was used to compare various perinatal outcomes between the user and non-user groups. Outcomes included LBW, FGR, preterm deliv• ery, abruptio placentae, low 5-minute Apgar scores, perinatal mortality, congenital malformations, and ce• sarean delivery rate. Finally, multiple logistic regression was used to control for potentially confounding vari• ables. Additional multivariate analysis was performed to compare the rates of abruptio placentae and low 5-minute Apgar scores in users with acute intoxication (positive urine drug screen within a week of delivery) versus non-users. For the purposes of this study, we used the following definitions. Prenatal care was defined as three or more prenatal visits, alcohol abuse as maternal consumption of four drinks per week, LBW as 2500 g or less, FGR as weight at the tenth percentile or less for gestational age, and preterm delivery as 36 weeks' gestation or less. The diagnosis of abruptio placentae was based on clinical recognition of vaginal bleeding, abdominal pain, con• sumptive coagulopathy, positive Kleihauer-Betke stain, or retroplacental clot. Gestational age was assigned using last menstrual period in conjunction with physi• cal and ultrasound examinations.
Results Of the women who were eligible, 86.5% consented to urine drug screens. White parturients were significantly more likely to decline testing 00.0% versus 5.8%) than black or "other" parturients. The prevalence of crack cocaine use during pregnancy in 1992 in our popula• tion, detected by urine cocaine screens, was 13.3%. Maternal demographic and prenatal data for users and non-users are summarized in Table 1. The group of crack cocaine users tended to be older, single, black (Figure 1), multiparous women. Crack cocaine users were significantly more likely than controls to abuse alcohol (23.6% versus 3.0%), to use tobacco (75.0% versus 16.2%), to weigh less than 100% of ideal body weight (35.6% versus 24.8%), and to receive inadequate prenatal care (58.0% versus 23.3%),
Sprauve et al
Crack Cocaine Use in Pregnancy
675
Table 2. Univariate Analysis of Selected Prenatal Outcomes in Users Versus Non-Users
Table 1. Selected Demographic Characteristics of Users Versus Non-Users Users 483)
Characteristic
(n =
Age (y) <18 18-34 >34 Marital status* Single Married Other Parity
o
1 2:2 Education* <12th 2:12th Prenatal care Adequate Inadequate Alcohol abuse Yes No Tobacco use" Yes No Ideal birth weight <100 percentile 2:100 percentile
Non-users 3158)
4(0.8%) 439 (90.9%) 40 (8.3%)
468 (14.8%) 2519 (79.8%) 171 (5.4%)
<.01
397 (82.2%) 37(7.7%) 49 (10.1%)
2211 (70.1%) 693 (22.0%) 252 (8.0%)
<.01
61 (12.6%) 96 (19.9%) 326(67.5%)
1163 (36.8%) 859 (27.2%) 1136 (36.0%)
<.01
118(25.9%) 338 (74.1%)
822(26.7%) 2258 (73.3%)
.61
203 (42.0%) 280(58.0%)
2421 (76.7%) 737(23.3%)
<.01
114 (23.6%) 369(76.4%)
94 (3.0%) 3064 (97.0%)
<.01
315 (75.0%) 105 (25.0%)
444 (16.2%) 2299 (83.8%)
<.01
141 (35.6%) 255 (64.4%)
733 (24.8%) 2222 (75.2%)
<.01
P < .01. There was no difference between the groups in the prevalence of hypertension 0.1% versus 1.2%). Table 2 summarizes the univariate analysis of obstet• ric and perinatal outcomes in users versus non-users. Crack cocaine users were significantly more likely than
:;:-:-;:2--------------1
100...--..
ClI
Non-users
Crude OR (95% CI)
Low birth weight Fetal growth reslriction Premature delivery Abruptio placentae Low 5-min Apgar score Fetal death Neonatal death Congenital malformations Cesarean delivery
31.3% 29.0% 28.2% 3.3% 7.9% 1.5% 1.0% 2.3% 18.0%
14.9% 13.0% 17.1% 1.1% 4.5% 1.4% 0.8% 3.6% 15.3%
2.59 (2.07, 3.23)* 2.74 (2.18, 3.44)" 1.90 (1.52, 2.38)* 2.97 (1.57, 5.58)* 1.82 (1.23, 2.67)* 1.07 (0.44, 2.49) 1.37 (0.46, 3.79) 0.62 (0.31, 1.19) 1.22 (0.94, 1.58)
OR
=
odds ratio; CI = confidence interval.
non-users to deliver LBW (OR 2.59; 95% CI 2.07, 3.23), growth restricted (OR 2.74; 95% CI 2.18, 3.44), and preterm infants (OR 1.90; 95% CI 1.52, 2.38). In addition, cocaine users were significantly more likely to have an abruption (OR 2.97; 95% CI 1.57, 5.58) and to deliver an infant with a 5-minute Apgar score less than 7 (OR 1.82; 95% CI 1.23, 2.67). No differences were found between the groups in the incidence of fetal death, neonatal death, congenital malformation, or cesarean delivery. To ensure that the increased risks of LBW, FGR, preterm delivery, abruptio placentae, and low 5-minute Apgar score among users were not attributable to confounding variables, we performed multiple logistic regression to adjust for potential confounders (Table 3). Antenatal crack cocaine use remained independently associated with delivery of LBW (adjusted OR 1.59; 95% CI 1.03, 2.43) and growth-restricted infants (adjusted OR 1.70; 95% CI 1.24, 2.32). However, the risks of preterm delivery (adjusted OR 0.88; 95% CI 0.63, 1.22), abruptio placentae (adjusted OR 1.41; 95% CI 0.64, 3.10), and low 5-minute Apgar score (adjusted OR 1.38; 95% Table 3. Adjusted Odds Ratios and Confidence Intervals for Selected Perinatal Outcomes in Users Versus Non-Users
71111
80
Variable
Crude OR
Adjusted OR (950/0 cn
40
Low birth weightt Fetal growth reslriction* Premature delivery§ Abruptio placentaell Low 5-min Apgar score'
2.59 2.74 1.90 2.97 1.82
1.59 (1.03,2.43)* 1.70 (1.24, 2.32)* 0.88 (0.63, 1.22) 1.41 (0.64,3.10) 1.38 (0.57, 2.30)
i
0
~
Users
* p < .05.
" Because some records had incomplete information, the number of cases in some categories varies.
80
Outcome
p
(n =
20
153
02
0
Figure 1. Racial breakdown of parturients who use crack cocaine and non-using parturients. The majority of parturients in the "other" category are Hispanic and Asian.
676 Sprauve et al
Crack Cocaine Use in Pregnancy
OR = odds ratio; CI = confidence interval. * p < .05. Independent covariates for each model are listed: t Alcohol, tobacco, <1000/0 ideal body weight, prenatal care, preterm delivery, age. *Alcohol, tobacco, <100% ideal body weight, hypertension, marital status. § Tobacco, <100% ideal body weight, hypertension, abruption, pre• natal care, age. I Tobacco, hypertension. 'i Hypertension, FGR, abruption.
Obstetrics & Gynecology
CI 0.57, 2.30) among crack cocaine users did not persist (Table 3). To evaluate the effects of acute crack cocaine use on intrapartum events, we compared the rate of abruption and low 5-minute Apgar score between users with a positive urine drug screen within a week of delivery and non-users. After controlling for hypertension and tobacco use, we found no difference between the groups in the rate of abruption (crude OR 3.34; adjusted OR 1.37; 95% CI 0.57, 3.30). However, after controlling for hypertension, FGR, and abruption, users with recent crack cocaine use were significantly more likely to deliver a neonate with a low 5-minute Apgar score than were non-users (crude OR 2.35; adjusted OR 2.04; 95% CI 1.13, 3.68).
Discussion Because many of the adverse perinatal outcomes asso• ciated with cocaine use can potentially be attributable to confounding factors, it is imperative that these variables be adjusted for in observational studies addressing this issue. After controlling for relevant covariates, we were able to show, in a large homogeneous prenatal popula• tion, an independent association between antenatal crack cocaine use and both LBW and FGR. These results are consistent with findings in several other stud• ies.8.10.15.16 On the other hand, Mastrogiannis et al 6 examined the relation between antenatal cocaine use and growth-retarded infants and found no association. However, that study included only 40 patients in the cocaine group and thus, their results may be attribut• able to a type II error. Cocaine has vasoconstrictive effects on the maternal uteroplacental vasculature, which reduce uterine blood flow and restrict nutrient delivery to the fetus. 17- 19 This is the mechanism postu• lated to cause diminished birth weight and FGR. A meta-analysis of 26 studies performed from 1987 to 1991 revealed an association between cocaine use and premature delivery, abruptio placentae, and low 5-minute Apgar score. 2 However, methodologic differ• ences among these studies weaken their comparability, and few of the studies controlled for potential con• founders. In addition, none of these studies distin• guished between different methods of cocaine use. In contrast to previous studies, ours controlled for poten• tial confounders including tobacco use, hypertension, and prenatal care, and we were unable to show an association between crack cocaine use and preterm delivery, abruption, or low 5-minute Apgar score. Our failure to find an association between abruption and crack cocaine use requires further exploration. Abruptio placentae is frequently reported as a compli• cation of antenatal cocaine use,2°·21 Placental pathologic
VOL. 89, NO.5, PART 1, MAY 1997
findings such as decidual vascular thickening, villous ischemic infarction, and intervillous hemorrhage have been reported and implicated as the cause of the in• creased incidence of abruption found in cocaine users. 20 After controlling for tobacco use, we did not find an independent association between abruption and ante• natal crack cocaine use. Our results are similar to those in several smaller studies that failed to find an associ• ation between cocaine use and abruption. 6.1o A possible explanation for this finding is that the clinically evident increased rate of abruption observed in cocaine-using parturients is due to acute cocaine intoxication or to concomitant tobacco use. To pursue this hypothesis more fully, we examined the rate of abruption in users with acute crack cocaine use (positive urine drug screen within a week of delivery) versus non-users, and were still unable to detect a significant difference between the groups. However, parturients with acute crack cocaine use were significantly more likely than non-users to deliver neonates with low 5-minute Apgar scores. In our analysis, abruption was independently associated with low 5-minute Apgar score. Thus, our inability to find an increase in the rate of abruption may be due to lack of recognition of subclinical placental abruption or to under-reporting of abruption at the time of delivery. Our study has several strengths. As a result of our policy of routine urine drug screening on pregnant patients at Grady Memorial Hospital, we had the op• portunity to capture a large sample of predominantly crack cocaine-using parturients. Ascertainment bias was minimized because approximately 87% of the preg• nant women who were eligible consented to urine drug screens, and misclassification was reduced because women were categorized by objective criteria and not patient recall. In addition, we were able to control for potential confounders in our analysis. It is important to acknowledge that our study has several limitations. First, some patients who tested negative on their initial screen had no additional testing until delivery. If these patients were screened through• out pregnancy, some of them may have tested positive. Unless they tested positive at delivery, these patients would be included in the control group, biasing the results toward the null hypothesis. Second, no attempt was made to quantify the amount, the frequency, or the pattern of cocaine use. In addition, cocaine users have a marked tendency to abuse more than one substance. 22 Unfortunately, we did not have sufficient data on other illicit drug use to include it in our analysis. The avail• able data on alcohol and tobacco use did not include quantity and pattern of use, increasing the possibility of a beta error. We were missing data on tobacco use in 13% of the patients; however, the missing data were distributed proportionately between the groups, and
Sprauve et al
Crack Cocaine Use in Pregnancy
677
these patients had similar demographic characteristics as those patients for whom data on tobacco use were available. Finally, although this study was performed on a largely homogeneous population, the lifestyle of the addicted pregnant woman is probably not compa• rable to that of non-drug users or occasional drug users. As addiction worsens, the need for more frequent use overwhelms all other considerations and may lead to behavioral patterns that jeopardize maternal and fetal well-being in a manner for which we may not be able to adjust. lO Future studies should assess the impact of antenatal intervention on improving outcome in this high-risk population. A recent retrospective cohort study using birth certificate data in New York City suggested that prenatal care among cocaine users decreased the risk of LBW in this population. 23 In our study, approximately 50% of cocaine users received minimal or no prenatal care. Inadequate or lack of prenatal care was an inde• pendent predictor of LBW. The potentially beneficial effects of prenatal care on adverse perinatal outcomes in cocaine-using parturients have yet to be characterized adequately. The greatest difficulty encountered in studying the effects of prenatal care on perinatal out• come is defining "adequate" prenatal care. Our institu• tion uses a comprehensive prenatal care plan for women identified as crack cocaine users. It employs a team experienced in psychosocial behavior, drug reha• bilitation, social services, community health, and nutri• tion. Whether this approach leads to improved perina• tal outcome is unknown. Given the estimated $500 million to $6.12 billion per year spent on caring for neonates exposed to cocaine during pregnancy, it is imperative to investigate the effectiveness of our current model of prenatal care as well as other intervention strategies, such as increased antepartum surveillance and outpatient peer counseling programs.
References 1. Roe DA, Little BB, Bawdon RE, Gilstrap LC. Metabolism of cocaine by human placentas: Implications for fetal exposure. Am J Obstet Gynecol 1990;163:715-8. 2. Glantz JC, Woods JR. Cocaine, heroin, and phencyclidine: Obstet• ric perspectives. Clin Obstet Gynecol 1993;36:279-95. 3. Calhoun Be, Watson PT. The cost of maternal cocaine abuse: I. Perinatal cost. Obstet GynecoI1991;78:731-4. 4. Phibbs C5, Bakman DA, Schwartz RM. The neonatal costs of maternal cocaine use. JAMA 1991;266:1521-6. 5. Chasnoff Il, Griffin DR, MacGregor S, Dirkes K, Bums KA. Tem• poral patterns of cocaine use in pregnancy. JAMA 1989;261:1741-4. 6. Mastrogiannis OS, Decavalas GO, Verma V, Tejani N. Perinatal outcome after recent cocaine usage. Obstet GynecoI1990;76:8-11.
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7. Chasnoff IJ, Burns WJ, Schnoll 5H, Burns KA. Cocaine use in pregnancy. N Engl J Med 1985;313:666-9. 8. Cherukuri R Minkoff H, Feldman J, Parekh A, Glass L. A cohort study of alkaloidal cocaine ("crack") in pregnancy. Obstet Gynecol 1988;72:147-51. 9. Handler A, Kistin N, Davis F, Ferre C. Cocaine use during pregnancy: Perinatal outcomes. Am J EpidemioI1991;133:818-25. 10. MacGregor 5N, Keith LG, Chasnoff IJ, Rosner MA, Chisum GM, Shaw P, et a!. Cocaine use during pregnancy: Adverse perinatal outcome. Am J Obstet Gynecol 1987;157:686-90. 11. Ryan L, Ehrlich 5, Finnegan L. Cocaine abuse in pregnancy: Effects on the fetus and newborn. Neurotoxicol TeratoI1987;9:295-9. 12. el-Fawal HA, Woods RW. Airway smooth muscle relaxant effects of the cocaine pyrolysis product, methylecgonidine. J Pharmacol Exp Ther 1995;272:991-6. 13. Lindsay MK, CarmichaelS, Peterson H, Risby J, Williams H, Klein L. The correlation between self-report of cocaine use and urine toxicology in an inner-city prenatal population. J Natl Med Assoc 1997;89:57-60. 14. Ambre J. The unnary excretion of cocaine and metabolites in humans: A kinetic analysis of published data. J Anal Toxicol 1985;9:241-4. 15. Bates CK. Medical risks of cocaine use. West J Med 1988;148:440-4. 16. Handler A, Kistin N, Davis F, Ferre C. Cocaine use during pregnancy: Perinatal outcomes. Am J EpidemioI1991;133:818-25. 17. Sherman WT, Gautien RF. Effects of certain drugs on perfused human placenta. Norepinephrine release by bradykinin. J Pharm Sci 1972;61:878-83. 18. Woods JR, Plessinger MA, Clark KE. Effect of cocaine on uterine blood fetal oxygenation. JAMA 1987;257:957-62. 19. Moore TR, Song J, Miller L, Key Te, Resnik R. Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus. Am J Obstet Gynecol 1986;155:883-8. 20. Acher D, Sachs BP, Tracey KJ, Wise WE. Abruptio placentae associated with cocaine use. Am J Obstet GynecoI1983;146:220-1. 21. Townsend RR, Laing Fe, Brooke J. Placental abruption associated with cocaine use. AJR Am J Roentgenol 1988;150:1339-40. 22. Chasnoff IJ. Cocaine and pregnancy: Clinical and methodologic issues. Clin Perinatol 1991;18:113-23. 23. Racine A, Joyce T, Anderson R. The association between prenatal care and birth weight among women exposed to cocaine in New York City. JAMA 1993;270:1581-6.
Address reprint requests to:
Margaret E. Sprauve, MD, MPH Department of Gynecology and Obstetrics Emory University School of Medicine 69 Butler Street, SE Atlanta, GA 30303
Received October 21, 1996. Received in revised form January 10, 1997. Accepted January 21, 1997. Copyright © 1997 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
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