PREGNANCY AND CANNABIS USE

Clin Chem. 2010 Sep;56(9):1442-50. Epub 2010 Jul 13.

Identifying prenatal cannabis exposure and effects of concurrent tobacco exposure on neonatal growth.
Gray TR, Eiden RD, Leonard KE, Connors GJ, Shisler S, Huestis MA.

Source
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.

Abstract
BACKGROUND: Cannabis is the most frequently used illicit drug among pregnant women, but data describing the effects of prenatal cannabis exposure and concurrent nicotine and cannabis exposures on neonatal growth are inconsistent. Testing of meconium, the first neonatal feces, offers objective evidence of prenatal cannabis exposure, but the relative ability of meconium testing and maternal self-report to identify affected neonates remains unclear. METHODS: Eighty-six pregnant women provided detailed self-reports of daily cannabis and tobacco consumption throughout pregnancy. Cannabinoids and tobacco biomarkers were identified in oral fluid samples collected each trimester and quantified in meconium at birth. RESULTS: Cannabis-using women were significantly more likely to also consume tobacco, and smoked similar numbers of cigarettes as non-cannabis-using tobacco smokers. As pregnancy progressed, fewer women smoked cannabis and those who continued to use cannabis reported smoking a smaller number of cannabis joints, but positive maternal oral fluid tests cast doubt on the veracity of some maternal self-reports. More neonates
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were identified as cannabis exposed by maternal self-report than meconium analysis, because many women quit cannabis use after the first or second trimester; meconium was more likely to be positive if cannabis use continued into the third trimester. Cannabis exposure was associated with decreased birth weight, reduced length, and smaller head circumference, even after data were controlled for tobacco coexposure. CONCLUSIONS: Prenatal cannabis exposure was associated with fetal growth reduction. Meconium testing primarily identifies prenatal cannabis exposure occurring in the third trimester of gestation. http://www.ncbi.nlm.nih.gov/pubmed/20628142

J Am Acad Child Adolesc Psychiatry. 2009 Dec;48(12):1173-81.

Intrauterine cannabis exposure affects fetal growth trajectories: the Generation R Study.
El Marroun H, Tiemeier H, Steegers EA, Jaddoe VW, Hofman A, Verhulst FC, van den Brink W, Huizink AC.

Source
Department of Child and Adolescent Psychiatry and the Generation R Study Group, Rotterdam, the Netherlands. h.marrounel@erasmusmc.nl

Abstract
OBJECTIVE: Cannabis is the most commonly consumed illicit drug among pregnant women. Intrauterine exposure to cannabis may result in risks for the developing fetus. The importance of intrauterine growth on subsequent psychological and behavioral child development has been demonstrated. This study examined the relation between maternal cannabis use and fetal growth until birth in a population-based sample. METHOD: Approximately 7,452 mothers enrolled during pregnancy and provided information on substance use and fetal growth. Fetal growth was determined using ultrasound measures in early, mid-, and late pregnancy. Additionally, birth weight was assessed.
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RESULTS: Maternal cannabis use during pregnancy was associated with growth restriction in midand late pregnancy and with lower birth weight. This growth reduction was most pronounced for fetuses exposed to continued maternal cannabis use during pregnancy. Fetal weight in cannabis-exposed fetuses showed a growth reduction of -14.44 g/week (95% confidence interval -22.94 to -5.94, p = .001) and head circumference (-0.21 mm/week, 95% confidence interval -0.42 to 0.02, p = .07), compared with nonexposed fetuses. Maternal cannabis use during pregnancy resulted in more pronounced growth restriction than maternal tobacco use. Paternal cannabis use was not associated with fetal growth restriction. CONCLUSIONS: Maternal cannabis use, even for a short period, may be associated with several adverse fetal growth trajectories.

BJOG. 2002 Jan;109(1):21-7.

Maternal use of cannabis and pregnancy outcome.

Fergusson DM, Horwood LJ, Northstone K; ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Source
Christchurch Health and Development Study, Christchurch School of Medicine, Christchurch Hospital, New Zealand.

Abstract
OBJECTIVE: To document the prevalence of cannabis use in a large sample of British women studied during pregnancy, to determine the association between cannabis use and social and lifestyle factors and assess any independent effects on pregnancy outcome. DESIGN: Self-completed questionnaire on use of cannabis before and during pregnancy. SAMPLE:
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Over 12,000 women expecting singletons at 18 to 20 weeks of gestation who were enrolled in the Avon Longitudinal Study of Pregnancy and Childhood. METHODS: Any association with the use of cannabis before and during pregnancy with pregnancy outcome was examined, taking into account potentially confounding factors including maternal social background and other substance use during pregnancy. MAIN OUTCOME MEASURES: Late fetal and perinatal death, special care admission of the newborn infant, birthweight, birth length and head circumference. RESULTS: Five percent of mothers reported smoking cannabis before and/or during pregnancy; they were younger, of lower parity, better educated and more likely to use alcohol, cigarettes, coffee, tea and hard drugs. Cannabis use during pregnancy was unrelated to risk of perinatal death or need for special care, but, the babies of women who used cannabis at least once per week before and throughout pregnancy were 216 g lighter than those of non-users, had significantly shorter birth lengths and smaller head circumferences. After adjustment for confounding factors, the association between cannabis use and birthweight failed to be statistically significant (P = 0.056) and was clearly non-linear: the adjusted mean birthweights for babies of women using cannabis at least once per week before and throughout pregnancy were 90 g lighter than the offspring of other women. No significant adjusted effects were seen for birth length and head circumference. CONCLUSIONS: The results of this study suggest that the use of cannabis during pregnancy was not associated with increased risk of perinatal mortality or morbidity in this sample. However, frequent and regular use of cannabis throughout pregnancy may be associated with small but statistically detectable decrements in birthweight.

European Journal of Pediatrics Volume 158, Number 6, 488-492, DOI: 10.1007/s004310051126

Substance misuse in early pregnancy and relationship to fetal outcome

R. A. Sherwood, J. Keating, V. Kavvadia, A. Greenough and T. J. Peters To establish the frequency of substance misuse in early pregnancy in an urban UK population, 807 consecutive positive pregnancy test urine samples were screened for a range of drugs, including cotinine as an indicator of maternal smoking habits. A positive test for cannabinoids was found in 117 (14.5%) samples. Smaller numbers of samples were positive for other drugs:- opiates (11), benzodiazepines (4), cocaine (3) and one each for amphetamines and methadone. Polydrug use was detected in nine individuals. Only two samples tested positive for ethanol. The proportion with a urine cotinine level indicative of active smoking was 34.3%. The outcome of the pregnancy was traced for 288 subjects. Cannabis use was associated with a lower gestational age at delivery (P<0.005), an increased risk of prematurity (P<0.02) and reduction in birth weight (P<0.002). Whilst maternal smoking was associated with a reduction in infant birth weight (P<0.05), this was less pronounced than the effect of other substance misuse. Conclusion This study suggests that one in six women in South London are using drugs in early pregnancy and that cannabinoid use is associated with a poorer pregnancy outcome.

Maternal use of cannabis and pregnancy outcome

1. 2. 3. 4. David M. Fergusson1, L. John Horwood1, Kate Northstone2,*, ALSPAC Study Team2

BJOG: An International Journal of Obstetrics & Gynaecology

Volume 109, Issue 1, pages 2127, January 2002 Objective To document the prevalence of cannabis use in a large sample of British women studied during pregnancy, to determine the association between cannabis use and social and lifestyle factors and assess any independent effects on pregnancy outcome.
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Design Self-completed questionnaire on use of cannabis before and during pregnancy. Sample Over 12,000 women expecting singletons at 18 to 20 weeks of gestation who were enrolled in the Avon Longitudinal Study of Pregnancy and Childhood. Methods Any association with the use of cannabis before and during pregnancy with pregnancy outcome was examined, taking into account potentially confounding factors including maternal social background and other substance use during pregnancy. Main outcome measures Late fetal and perinatal death, special care admission of the newborn infant, birthweight, birth length and head circumference. Results Five percent of mothers reported smoking cannabis before and/or during pregnancy; they were younger, of lower parity, better educated and more likely to use alcohol, cigarettes, coffee, tea and hard drugs. Cannabis use during pregnancy was unrelated to risk of perinatal death or need for special care, but, the babies of women who used cannabis at least once per week before and throughout pregnancy were 216g lighter than those of non-users, had significantly shorter birth lengths and smaller head circumferences. After adjustment for confounding factors, the association between cannabis use and birthweight failed to be statistically significant (P= 0.056) and was clearly non-linear: the adjusted mean birthweights for babies of women using cannabis at least once per week before and throughout pregnancy were 90g lighter than the offspring of other women. No significant adjusted effects were seen for birth length and head circumference. Conclusions The results of this study suggest that the use of cannabis during pregnancy was not associated with increased risk of perinatal mortality or morbidity in this sample. However, frequent and regular use of cannabis throughout pregnancy may be associated with small but statistically detectable

decrements

J Pediatr. 1990 Oct;117(4):622-6.

Neonatal body proportionality and body composition after in utero exposure to cocaine and marijuana.
Frank DA, Bauchner H, Parker S, Huber AM, Kyei-Aboagye K, Cabral H, Zuckerman B.

Source
Division of Developmental and Behavioral Pediatrics, Boston City Hospital, Boston University School of Medicine, MA 02118.

Abstract
The relationship of maternal use of marijuana and cocaine during pregnancy to measures of neonatal body proportionality and body composition was assessed in a multiethnic sample of 1082 newborn infants. Maternal use of marijuana and cocaine
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during pregnancy was ascertained by self-report and by an enzyme-multiplied immunoassay technique for screening of urine samples obtained prenatally and again post partum. After each substance was analytically controlled for use of the other and for other potentially confounding variables, detection of marijuana metabolites in maternal urine was associated (p less than 0.05) with depressed mean arm muscle circumference and nonfat area of the arm but not with any measure of neonatal fatness. In contrast, detection of cocaine in maternal urine was associated (p less than 0.05) with decrements of subscapular fat folds and of the fat and nonfat areas of the arm. Although both substances were associated with depressed birth weight, there was no decrement of neonatal ponderal index or of the arm circumference/head circumference ratio in association with exposure to either substance. We conclude that both marijuana exposure and cocaine exposure during pregnancy are associated with symmetric intrauterine growth retardation, but that deficits are in differing compartments of intrauterine growth. These findings suggest that marijuana may retard fetal growth through maternal-fetal hypoxia, whereas cocaine may alter nutrient transfer to the fetus and fetal metabolism.

N Engl J Med. 1989 Mar 23;320(12):762-8.

Effects of maternal marijuana and cocaine use on fetal growth.

Zuckerman B, Frank DA, Hingson R, Amaro H, Levenson SM, Kayne H, Parker S, Vinci R, Aboagye K, Fried LE, et al.

Source
Division of Developmental and Behavioral Pediatrics, Boston City Hospital, MA 02118.

Abstract
To investigate the effects on infants of the use of marijuana and cocaine during pregnancy and to compare the importance of urine assays with that of interviews in ascertaining drug use, we prospectively studied 1226 mothers, recruited from a general prenatal clinic, and their infants. On the basis of either interviews or urine assays conducted prenatally or post partum, 27 percent of the subjects had used marijuana during pregnancy and 18 percent had used cocaine. When only positive urine assays were considered, the corresponding values were 16 percent and 9 percent, respectively. When potentially confounding variables were controlled for in the analysis, the infants whose mothers had positive urine assays for marijuana, as compared with the infants whose mothers were negative according to both interviews and urine assays, had a 79-g decrease in birth weight (P = 0.04) and a 0.5-cm decrement in length (P = 0.02). Women who had positive assays for cocaine, as compared with nonusers, had infants with a 93-g decrease in birth weight (P = 0.07), a 0.7-cm decrement in length (P = 0.01),
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and a 0.43-cm-smaller head circumference (P = 0.01). To compare our findings with those of other investigators who did not use urine assays, we repeated the analyses, considering only self-reported use of marijuana (23 percent) and cocaine (13 percent). There were no significant associations between such use as determined by interviews alone and any of the measures of outcome. We conclude that the use of marijuana or cocaine during pregnancy is associated with impaired fetal growth and that measuring a biologic marker of such use is important to demonstrate the association.

Early Hum Dev. 2010 Apr;86(4):231-6. Epub 2010 May 6.

A prospective study on intrauterine cannabis exposure and fetal blood flow.

El Marroun H, Tiemeier H, Steegers EA, Roos-Hesselink JW, Jaddoe VW, Hofman A, Verhulst FC, van den Brink W, Huizink AC.

Source
Erasmus Medical Center, The Netherlands.

Abstract
BACKGROUND: Cannabis is commonly used among pregnant women. It is unclear whether cannabis exposure causes hemodynamic modifications in the fetus, like tobacco does. AIMS: This study aims to ascertain fetal blood redistribution due to intrauterine cannabis exposure.

METHODS: This study was embedded in the Generation R Focus Study, a population-based cohort of parents and children followed from pregnancy onwards. In late pregnancy, fetal hemodynamics was assessed with ultrasound measurements in cannabis-exposed and non-exposed fetuses. Pregnant women reported about substance use during pregnancy. A distinction was made between continued cannabis use (n=9), cannabis use only in early pregnancy (n=14), continued tobacco use (n=85), tobacco use only in early pregnancy (n=92), and no tobacco or cannabis use during pregnancy (n=85).
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RESULTS: Continued cannabis use was associated with an increased pulsatility and resistance index of the uterine artery, while discontinued cannabis use was associated with a decreased pulsatility, and resistance index, as compared to controls. Additionally, continued cannabis exposure resulted in a significantly higher uterine pulsatility index and uterine resistance index compared to tobacco exposure. Continued cannabis use was found to be associated with a smaller aortic diameter, as well. No association between intrauterine cannabis exposure and the fetal cerebral vascular system was found.

CONCLUSIONS: Our findings suggest that intrauterine cannabis exposure was associated with changes in hemodynamic programming of the vascular system of the fetus in late pregnancy mainly due to tobacco exposure, but intrauterine cannabis exposure did demonstrate a specific effect on the uterine blood flow. http://www.ncbi.nlm.nih.gov/pubmed/20451334

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