Woman, alcohol and environment: Emerging risks for health

Alcohol drinking is one of the most relevant problems in Western Countries but the negative effects of alcohol misuse are often neglected or underestimated with serious consequences for public health. Over the last few years a rapid growth in the number of drinking females and the decrease of their age of first use, have increased the health risk for women and their offspring. Moreover, modern environments facilitate pollutants exposure, further escalating the health risks due to lifestyle habits. This review takes into account the peculiarities of alcohol effects on female health and the risks of teratogenic effects. The possible interaction between alcohol and pollutants exposure is also discussed. The role of biomarkers against alcohol-related damage is presented as an invaluable clinical tool, including early intervention, treatment monitoring and, above all, prevention of prenatal non-reversible damage. Recent alcohol studies show the greater severity of alcohol damage in female subjects and the need of gender-targeted intervention.     

Smoking during pregnancy and attention-deficit/hyperactivity disorder, predominantly inattentive type: a case-control study

OBJECTIVE: Few previous studies assessed specifically attention-deficit/hyperactivity disorder, predominantly inattentive subtype (ADHD-I) in nonreferred samples. This study investigated the association between ADHD-I and prenatal exposure to nicotine. METHOD: In a case-control study performed between September 2002 and April 2005, we assessed a nonreferred Brazilian sample of 100 children and adolescents with ADHD-I and 100 non-ADHD controls (6-18 years old). Cases and controls, matched by gender and age, were screened using teacher reports in the Swanson, Nolan, and Pelham-IV (SNAP-IV) scale. They were systematically evaluated through structured diagnostic interviews. Prenatal exposure to nicotine and potential confounding factors were evaluated by direct interview with mothers. RESULTS: Adjusting for confounding factors (maternal ADHD, oppositional defiant disorder, birth weight, and alcohol use during pregnancy), children whose mothers smoked>or=10 cigarettes per day during pregnancy presented a significantly higher odds ratio for ADHD-I than children who were not exposed to nicotine during pregnancy (odds ratio 3.44; 95% confidence interval 1.17-10.06). Dimensional analyses showed significantly higher inattentive scores in subjects whose mothers smoked>or=10 cigarettes per day than in others after adjusting for confounding factors (p=.002). CONCLUSIONS: In a nonreferred sample, the authors expanded to ADHD-I previous findings documenting the association between prenatal exposure to nicotine and broadly defined ADHD in clinical samples.     

Offspring from families at high risk for alcohol dependence: increased body mass index in association with prenatal exposure to cigarettes but not alcohol

The prevalence of overweight and obese children is increasing, a tendency that can be expected to increase the risk of adverse outcomes in adulthood. The aim of this study was to determine if prenatal exposure to alcohol, cigarettes, and street drugs would be associated with differences in body mass index (BMI) in childhood and adolescence in offspring from families at high and low genetic risk for developing alcohol dependence. Annual follow-up of offspring (N = 288) provided 1200 height and weight assessments for analysis. Maternal substance use data were available for 235 offspring from families stratified for familial/genetic risk for alcohol dependence (high or low risk), providing the opportunity to assess prenatal exposure and familial/genetic risk in relation to BMI in the offspring. When data were grouped by the presence or absence of any prenatal cigarette exposure, a significant difference in offspring BMI was seen for 8- to 11-year-olds. Significant group differences were also seen at ages 12-15 and 16-18 years. A dose-response relationship between cigarette use by the mother and offspring BMI was also seen. With the strong tendency for individuals who are overweight in childhood and adolescence to become overweight adults, prenatal exposure to nicotine may be a harbinger of increased risk for numerous adult-onset, weight-related health problems.     

Maternal smoking during pregnancy and adult male criminal outcomes

BACKGROUND: Perinatal risk factors are related to persistent and violent criminal outcomes. Prenatal maternal smoking may represent an additional perinatal risk factor for adult criminal outcomes. Our study examines maternal smoking during pregnancy as a predictor of offspring crime in the context of a prospective, longitudinal design. METHODS: Subjects were a birth cohort of 4169 males born between September 1959 and December 1961 in Copenhagen, Denmark. During the third trimester of pregnancy, mothers self-reported the number of cigarettes smoked daily. When the male offspring were 34 years of age, their arrest histories were checked in the Danish National Criminal Register. Additional data were collected concerning maternal rejection, socioeconomic status, maternal age, pregnancy and delivery complications, use of drugs during pregnancy, paternal criminal history, and parental psychiatric hospitalization. RESULTS: Results indicate a dose-response relationship between amount of maternal prenatal smoking and arrests for nonviolent and violent crimes. Maternal prenatal smoking was particularly related to persistent criminal behavior rather than to arrests confined to adolescence. These relationships remained significant after potential demographic, parental, and perinatal risk confounds were controlled for. CONCLUSIONS: Maternal prenatal smoking predicts persistent criminal outcome in male offspring. This relationship has not been accounted for by related parental characteristics or perinatal problems. Potential physiologic or central nervous system mediators between maternal smoking during pregnancy and offspring criminal outcomes need further study.     

Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy

OBJECTIVE: To address the putative association between attention-deficit hyperactivity disorder (ADHD) and prenatal exposure to maternal cigarette smoking, drugs of abuse, and alcohol attending to potential confounding by familial ADHD, maternal depression, conduct disorder, and indicators of social adversity in the environment. METHOD: A retrospective, hospital-based, case-control study was conducted with 280 ADHD cases and 242 non-ADHD controls of both genders. The case and control children and their relatives were systematically assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of prenatal exposure to substance use and ADHD. RESULTS: ADHD cases were 2.1 times (95% confidence interval = 1.1-4.1;p = .02) more likely to have been exposed to cigarettes and 2.5 times (95% confidence interval = 1.1-5.5; p = .03) more likely to have been exposed to alcohol in utero than were the non-ADHD control subjects. Adjustment by familial psychopathology, Rutter's indicators of social adversity, and comorbid conduct disorder did not account for the effect of prenatal exposure to alcohol or the products of cigarettes. CONCLUSIONS: ADHD may be an additional deleterious outcome associated with prenatal exposure to alcohol independently of the association between prenatal exposure to nicotine and smoke products and other familial risk factors for the disorder.     

Clinical importance of age at first drink in a group of young men

A survey of 1,012 university men aged 21 to 25 years revealed that age at first drink varied inversely with alcohol consumption and frequency of drinking, incidence of alcohol-related problems, and incidence of drug use and associated problems.     

Prenatal nicotine exposure and child behavioural problems

In utero exposure to tobacco smoke has been related to numerous adverse health effects in new-borns, infants, children, adolescents and adults. The aim of this review was to summarise findings on prenatal nicotine exposure and its relationship with behavioural problems in the offspring. The majority of studies, and especially several recent epidemiological studies, observed a higher likelihood for attention-deficit/hyperactivity disorder (ADHD) or ADHD symptoms in exposed subjects. However, both human and animal studies have failed to provide clear evidence on causality. Existing literature on studies investigating the association between prenatal nicotine exposure and conduct or externalising problems in the offspring suggests a causal effect. The establishment of a final conclusion concerning the relationship between prenatal nicotine exposure and internalising problems in the offspring is complicated by insufficient data and mixed results in epidemiological studies. Prenatal nicotine exposure has been associated with altered brain structure and function in human offspring, and a proposed biological mechanism is related to nicotine’s adverse influence on neurotransmitter systems during brain development. In conclusion, establishing a statement on the causality of the relationship between prenatal nicotine exposure and behavioural problems in children remains a challenging task. Nevertheless, considering the results of an increasing number of studies which link prenatal exposure to nicotine to externalising problems applying different methodologies to account for confounding and in view of other adverse health effects known to be caused by this exposure, parents should consider smoking cessation.     

Twelve-year follow-up of children exposed to alcohol in utero

Eighty-two women who were consuming alcohol while pregnant attended a special clinic at the University Central Hospital, Helsinki with the aim of reducing heavy drinking during pregnancy. The children born to these women were followed up regularly. During their preschool years the children were assessed to have fetal alcohol syndrome, fetal alcohol effects, alcohol-related neurodevelopmental disorder, pre- and/or postnatal growth retardation, or they were assessed to have normal cognitive and somatic growth. Of the original children, 70 of 82 could be traced at the age of 12 years. Through semistructured interview and contact with the health and social care authorities, information was gathered about schooling, family structure, whether help had been sought for behavioural difficulties and major adverse events in the family. The longer the intrauterine alcohol exposure and the more severe the diagnosis related to prenatal alcohol exposure, the more often the children required special education, were temporarily or permanently taken into care, and had behavioural problems. There is a considerable need for prolonged multidisciplinary follow-up and support of all children whose mothers have not been able to reduce drinking in early pregnancy, whether or not cognitive disturbances are evident in early childhood.     

Binge drinking during pregnancy as a predictor of psychiatric disorders on the Structured Clinical Interview for DSM-IV in young adult offspring

OBJECTIVE: This study explored the extent to which the high frequency of psychiatric problems reported in clinical groups with fetal alcohol spectrum disorders might also be observed in a nonclinical group of young adults and the psychiatric conditions that are related to prenatal alcohol exposure in this group. METHOD: From a longitudinal prospective study beginning with interviews of 1,529 pregnant women, a birth cohort of about 500 newborns was chosen to include all of the most heavily alcohol exposed plus a sampling of the continuum of alcohol exposures from total abstinence through heavy drinking. At an average age of 25.7 years, 400 members of this birth cohort were administered valid Structured Clinical Interviews for DSM-IV (SCID), including both the SCID for axis I disorders and the SCID for axis II personality disorders. RESULTS: The odds of the appearance of six psychiatric disorders and traits were more than double in adults exposed to one or more binge alcohol episodes in utero. Three of these six odds ratios were uniformly stable against confounding: axis I substance dependence or abuse disorders and axis II passive-aggressive and antisocial personality disorders or traits. CONCLUSIONS: Prenatal exposure to alcohol may be a risk factor for specific psychiatric disorders and traits in early adulthood, even in a nonclinical group.     

Behavioral and neural consequences of prenatal exposure to nicotine

OBJECTIVE: To review evidence for the neurodevelopmental effects of in utero exposure to nicotine. Concerns about long-term cognitive and behavioral effects of prenatal exposure to nicotine arise from reports of increased rates of disruptive behavioral disorders in children whose mothers smoked during pregnancy. The relatively high rate of tobacco smoking among pregnant women (25% of all pregnancies in the U.S.) underlines the seriousness of these concerns. METHOD: This review examines the largest and most recent epidemiological and clinical studies that investigated the association of prenatal nicotine exposure with health, behavioral, and cognitive problems. Because of the numerous potential confounding variables in human research, findings from animal studies, in which environmental factors are strictly controlled, are also discussed. Finally, neural and molecular mechanisms that are likely to underlie neurodevelopmental disruptions produced by prenatal nicotine exposure are outlined. RESULTS: A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors. Despite the wide variability of experimental paradigms used in animal studies, common physical and behavioral effects of prenatal exposure to nicotine have been observed, including low birth weight, enhanced locomotor activity, and cognitive impairment. Finally, disturbances in neuronal pathfinding, abnormalities in cell proliferation and differentiation, and disruptions in the development of the cholinergic and catecholaminergic systems all have been reported in molecular animal studies of in utero exposure to nicotine. CONCLUSIONS: Prenatal exposure to nicotine may lead to dysregulation in neurodevelopment and can indicate higher risk for psychiatric problems, including substance abuse. Knowledge of prenatal exposure to nicotine should prompt child psychiatrists to closely monitor at-risk patients.     

Commissural size in neonatal rats: effects of sex and prenatal alcohol exposure

Sex differences have been reported in the size of the adult corpus callosum in both humans and rodents. This experiment investigated whether sex and/or different prenatal treatment conditions would influence commissural size at birth. Male and female 3-day-old Long Evans rats were selected from one of three prenatal treatment histories: prenatal alcohol-exposed (35% ethanol-derived calories, 35% EDC), nutritional control (0% ethanol-derived calories, 0% EDC) or standard control (lab chow). Midline sagittal areas of the corpus callosum and the anterior commissure were determined for these subjects. Male control subjects had significantly larger callosal areas than females. Prenatal alcohol exposure significantly abolished this sexual dimorphism, with 35% EDC males having a significantly smaller callosal area than males from both control groups. This effect was independent of prenatal treatment differences in body or brain size. There were no significant sex differences in the midline sagittal area of the anterior commissure, nor were there any apparent effects of prenatal treatment on this measure. These results indicate that sex differences in the size of the corpus callosum are present at birth. Since a difference in myelination cannot account for this difference in area, there may be a sex difference in the number of fibers or in the average fiber size. Additionally, the effects of prenatal alcohol exposure on male, but not female, offspring suggest that this alcohol-related birth defect is hormonally mediated.     

Impact of age at first drink on vulnerability to alcohol-related problems: Testing the marker hypothesis in a prospective study of young adults

There is ample evidence that the early initiation of alcohol use is a risk factor for the development of later alcohol-related problems. The purpose of the current study was to examine whether this association can be explained by indicators of a common underlying susceptibility or whether age at drinking onset may be considered as an independent predictor of later drinking behavior, suggesting a potential causal relationship. Participants were drawn from a prospective cohort study of the long-term outcomes of early risk factors followed up from birth onwards. Structured interviews were administered to 304 participants to assess age at first drink and current drinking behavior. Data on risk factors, including early family adversity, parental alcohol use, childhood psychopathology and stressful life events, were repeatedly collected during childhood using standardized parent interviews. In addition, information on genotype was considered. Results confirmed previous work demonstrating that hazardous alcohol consumption is related to early-adolescent drinking onset. A younger age of first drink was significantly predicted by 5-HTTLPR genotype and the degree of preceding externalizing symptoms, and both factors were related to increased consumption or harmful alcohol use at age 19. However, even after controlling for these potential explanatory factors, earlier age at drinking onset remained a strong predictor of heavy alcohol consumption in young adulthood. The present longitudinal study adds to the current literature indicating that the early onset - adult hazardous drinking association cannot solely be attributed to shared genetic and psychopathologic risk factors as examined in this study.     

Effects of prenatal alcohol exposure on brain-derived neurotrophic factor and its receptor tyrosine kinase B in offspring

Prenatal alcohol exposure produces many developmental defects in the central nervous system. The underlying molecular mechanism, however, has not been fully understood. The present study was undertaken to examine the effects of prenatal alcohol exposure on brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in offspring. The pregnant Sprague-Dawley rats received 1 or 3 g/kg of alcohol or an isocaloric solution by intragastric intubation once a day from gestational day (GD) 5 to GD 20. On postnatal day 7-8, pups were killed and the hippocampus, striatum, cortex, and cerebellum dissected out. Levels of BDNF mRNA and proteins, total TrkB proteins and receptor phosphorylation were measured. The results showed that prenatal alcohol exposure at the dose of 1 g/kg/day did not significantly affect BDNF protein levels in any region examined. However, administration of alcohol at the dose of 3 g/kg/day markedly reduced levels of BDNF protein and mRNA in the cortex and hippocampus of offspring. Western blotting showed that prenatal alcohol exposure at the dose of 3 g/kg/day also inhibited TrkB phosphorylation in the hippocampus although no changes in total TrkB protein levels were observed in any region examined. Our data suggest that prenatal alcohol exposure alters both presynaptic and postsynaptic BDNF function in certain brain areas of offspring. These alterations in BDNF function may contribute to the development of alcohol-related birth defects.     

Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986

Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036–0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96–1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07–1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis.     

Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring

Teratological investigations have demonstrated that agents that are relatively harmless to the mother may have significant negative consequences to the fetus. Among these agents, prenatal alcohol, nicotine or cannabis exposure have been related to adverse offspring outcomes. Although there is a relatively extensive body of literature that has focused upon birth and behavioral outcomes in newborns and infants after prenatal exposure to maternal smoking, drinking and, to a lesser extent, cannabis use, information on neurobehavioral and cognitive teratogenic findings beyond these early ages is still quite limited. Furthermore, most studies have focused on prenatal exposure to heavy levels of smoking, drinking or cannabis use. Few recent studies have paid attention to low or moderate levels of exposure to these substances. This review endeavors to provide an overview of such studies, and includes animal findings and potential mechanisms that may explain the mostly subtle effects found on neurobehavioral and cognitive outcomes. It is concluded that prenatal exposure to either maternal smoking, alcohol or cannabis use is related to some common neurobehavioral and cognitive outcomes, including symptoms of ADHD (inattention, impulsivity), increased externalizing behavior, decreased general cognitive functioning, and deficits in learning and memory tasks.     

Adolescent Initiation of Drug Use: Effects of Prenatal Cocaine Exposure

ObjectiveTo investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use.MethodData are from a longitudinal study of PCE in which women and their offspring were assessed throughout childhood. Adolescents were interviewed at 15 years about their age at initiation of alcohol, marijuana, and tobacco. The sample consisted of 214 adolescents and their caregivers: 50% was of white ethnicity, and 50% African American.ResultsFirst trimester cocaine exposure significantly predicted earlier adolescent marijuana and alcohol initiation. The hazard of marijuana and alcohol initiation among exposed adolescents was almost two times greater than among nonexposed adolescents, adjusting for other significant factors. There were no differences in tobacco initiation. Other significant predictors of adolescent drug use were family history of alcohol problems, exposure to violence, and childhood maltreatment.ConclusionsCocaine exposure during early pregnancy was associated with initiation of marijuana and alcohol use. Exposure to violence, childhood maltreatment, and familial factors also predicted adolescent initiation, but did not mitigate the effects of PCE. The combination of these risk factors has significant implications for the development of later substance use, social, and psychiatric problems.     

Sexually dimorphic behavioral and brain asymmetries in neonatal rats: effects of prenatal alcohol exposure

Behavioral and neuroanatomical asymmetries were assessed in 3-day-old male and female rat pups chosen from litters whose dams had received one of 3 prenatal treatments: 35% ethanol-derived calories, pair-fed control, or lab chow control. Behavioral laterality was assessed by observing the preferred tail bias on postnatal (PN) day 1. On PN day 3, brains were sectioned and morphometric analyses conducted for total brain volume, left and right neocortical volumes, and left and right hippocampal volumes. Prenatal alcohol exposure altered the population proportions of left, right and neutral tail biases in male pups on PN day 1. Female pups were affected by both prenatal alcohol exposure and maternal undernutrition/stress of pair-feeding. Prenatal alcohol exposure decreased body weight and total brain volume, but increased the brain volume/body weight ratio compared to both control groups. Prenatal alcohol exposure also reduced the volumes of the hippocampus and neocortex, with the greatest proportional reduction found in the volume of the anterior neocortex. A left-right anterior neocortical asymmetry was observed, with tail bias, prenatal treatment and sex all significant factors. Alcohol-exposed males showed a 'feminized' asymmetry. These results demonstrate that a sexually dimorphic cerebral asymmetry can be detected at birth in rats; this asymmetry appears to be related to a postural position bias. The reversal of normal interhemispheric relations by prenatal alcohol exposure in male offspring suggested that the in utero hormonal milieu modulates the development of cerebral lateralization.     

Prenatal nicotine exposure impairs beta-adrenergic function: persistent chronotropic subsensitivity despite recovery from deficits in receptor binding

Gestational exposure to nicotine has been shown to interfere with biochemical markers of development of central and peripheral noradrenergic activity. The current study examines the development and function of cardiac beta-adrenergic receptors in the offspring of pregnant rats given nicotine infusions of 6 mg/kg/day from gestational days 4 through 20, administered by subcutaneously implanted osmotic minipumps. Prenatal nicotine exposure delayed the development of beta-adrenergic receptor binding capabilities, as assessed with [125I]pindolol in membrane preparations from heart and kidney. The deficits in receptor binding were associated with marked subsensitivity of chronotropic responses to administration of a beta-adrenergic agonist, isoproterenol. Although the effects on receptor binding resolved after weaning, functional deficiencies in responsiveness to isoproterenol or to preganglionic electrical stimulation of sympathetic nerves to the heart persisted into adulthood. These results indicate that prenatal exposure to nicotine produces long-term alterations in adrenergic responsiveness of sympathetic target tissues.     

Poor response inhibition as a predictor of problem drinking and illicit drug use in adolescents at risk for alcoholism and other substance use disorders

OBJECTIVE: To evaluate the predictive power of executive functions, in particular, response inhibition, in relation to alcohol-related problems and illicit drug use in adolescence. METHOD: A total of 498 children from 275 families from a longitudinal high-risk study completed executive function measures in early and late adolescence and lifetime drinking and drug-related ratings at multiple time points including late adolescence (ages 15-17). Multi-informant measures of attention-deficit/hyperactivity disorder and conduct disorder were obtained in early childhood (ages 3-5), middle childhood, and adolescence. RESULTS: In multilevel models, poor response inhibition predicted aggregate alcohol-related problems, the number of illicit drugs used, and comorbid alcohol and drug use (but not the number of drug-related problems), independently of IQ, parental alcoholism and antisocial personality disorder, child attention-deficit/hyperactivity disorder and conduct symptoms, or age. Multivariate models explained 8% to 20% of residual variance in outcome scores. The incremental predictive power of response inhibition was modest, explaining about 1% of the variance in most outcomes, but more than 9% of the residual variance in problem outcomes within the highest risk families. Other measured executive functions did not independently predict substance use onset. CONCLUSION: Models of alcoholism and other drug risks that invoke executive functions may benefit from specifying response inhibition as an incremental component.     

Relationship of maternal smoking during pregnancy with criminal arrest and hospitalization for substance abuse in male and female adult offspring.

OBJECTIVE: Maternal prenatal smoking has been found to be related to externalizing behavior problems in male offspring, but this relationship has rarely been examined in female offspring. Preliminary evidence suggests that maternal prenatal smoking may be particularly related to antisocial behavior outcomes in male offspring and substance abuse problems in female offspring. This study attempted to replicate these findings in a large-scale, longitudinal community cohort study. METHOD: Subjects were a birth cohort of 4,169 male and 3,943 female offspring born between 1959 and 1961 in Copenhagen, Denmark. During the third trimester of pregnancy, the subjects' mothers self-reported the number of cigarettes smoked on a daily basis. When the offspring were adults, their criminal arrest histories and psychiatric hospitalizations for substance abuse were checked in national registers. Additional data were collected concerning maternal rejection of the infant, socioeconomic status, maternal age, pregnancy and delivery complications, use of drugs in pregnancy, paternal criminal history, and parental psychiatric hospitalization. RESULTS: Results indicate a dose-response relationship between the amount of maternal prenatal smoking and both criminal arrest and psychiatric hospitalization for substance abuse in male and female offspring. These relationships remained significant after potential demographic, parental, and perinatal risk confounds were controlled. Hospitalization of offspring for substance abuse mediated the relationship between maternal prenatal smoking and criminal arrest for female but not for male offspring. CONCLUSIONS: Maternal prenatal smoking is related to criminal and substance abuse outcomes in male and female offspring. Higher rates of index arrests for female offspring may be related to their substance abuse problems.