School-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5-Year Follow-Up from the Infant Development, Environment, and Lifestyle Study.

OBJECTIVE: To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years and the extent to which early adversity mediated this relationship. STUDY DESIGN: The multicenter, longitudinal Infant Development, Environment, and Lifestyle study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5-year follow-up, 290 children with complete Child Behavior Checklist data and an early adversity index score were available for analysis (n = 146 exposed). RESULTS: PME was significantly associated with an increased early adversity index score (P < .001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P < .05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant. CONCLUSIONS: Though PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems.

Prenatal methamphetamine exposure and neonatal and infant neurobehavioral outcome: results from the IDEAL study.

BACKGROUND: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How MA use during pregnancy affects neonatal and infant neurobehavior is unknown. METHODS: The Infant Development, Environment, and Lifestyle (IDEAL) study screened 34,833 subjects at 4 clinical centers. Of the subjects, 17,961 were eligible and 3705 were consented, among which 412 were enrolled for longitudinal follow-up. Exposed subjects were identified by self-report and/or gas chromatography/mass spectroscopy (GC/MS) confirmation of amphetamine and metabolites in meconium. Comparison subjects were matched (race, birth weight, maternal education, insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, and marijuana use, but excluded use of opiates, lysergic acid diethylamide, or phencyclidine. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life and again at 1 month to 380 enrollees (185 exposed, 195 comparison). Analysis of variance (ANOVA) tested exposure effects on NNNS summary scores at birth and 1 month. General linear model (GLM) repeated-measures analysis assessed the effect of MA exposure over time on the NNNS scores with and without covariates. RESULTS: By 1 month of age, both groups demonstrated higher quality of movement (P = .029), less lethargy (P = .001), and fewer asymmetric reflexes (P = .012), with no significant differences in NNNS scores between the exposed and comparison groups. Over the first month of life, arousal increased in exposed infants but decreased in comparison infants (P = .031) and total stress was decreased in exposed infants, with no change in comparison infants (P = .026). CONCLUSIONS: Improvement in total stress and arousal were observed in MA-exposed newborns by 1 month of age relative to the newborn period.

Reactivity and regulation of motor responses in cocaine-exposed infants.

UNLABELLED: Effects of prenatal exposure to cocaine on the reactivity and regulation of the motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants and 487 non-exposed comparison infants were coded by examiners masked to exposure status. Exposure status was determined by meconium assay and maternal self-report of prenatal cocaine use. Infants were presented with a series of 17 visual, auditory and tactile stimuli for 30-s each. Intensity and latency of limb movement responses on a subset of items were analyzed to test the following hypotheses: CE infants are more active in general; CE infants exhibit increased movement levels for a larger proportion of time in response to stimulation; the motor systems of CE infants are more reactive to stimulation (e.g., shorter latencies to respond); and CE infants are poorer regulators of the motor system. RESULTS: CE infants were not more active in general and data do not indicate a more highly reactive motor system. However, CE infants exhibited increased movement levels for a larger proportion of time in response to stimulation. Additional analysis of movement exhibited during three tactile items found increased movement lability in CE infants and different patterns of responding, suggesting that the effects of prenatal cocaine exposure on the motor system may vary by context. Covariate effects for tobacco, alcohol, and marijuana are also reported.

Risk of neurobehavioral disinhibition in prenatal methamphetamine-exposed young children with positive hair toxicology results.

BACKGROUND: The objective was to evaluate the effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. METHODS: Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa, and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child's neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared with child hair results. RESULTS: A total of 264 children were evaluated. Significantly more PME children (n = 133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n = 131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared with PME children without postnatal exposure. CONCLUSIONS: Child hair testing offered a noninvasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years.

Prenatal substance exposure: neurobiologic organization at 1 month.

OBJECTIVE: To examine the autonomic nervous system and neurobehavioral response to a sustained visual attention challenge in 1-month-old infants with prenatal substance exposure. STUDY DESIGN: We measured heart rate, respiratory sinus arrhythmia, and neurobehavior during sustained visual orientation tasks included in the Neonatal Intensive Care Unit Network Neurobehavioral Scale in 1129 1-month-old infants with prenatal substance exposure. Four groups were compared: infants with prenatal cocaine and opiate exposure, infants with cocaine exposure, infants with opiate exposure, and infants with exposure to other substances (ie, alcohol, marijuana, and tobacco). RESULTS: The infants with prenatal exposure to both cocaine and opiates had the highest heart rates and lowest levels of respiratory sinus arrhythmia during a sustained visual attention challenge compared with the other 3 groups. Infants with prenatal cocaine and opiate exposure had poorer quality of movement and more hypertonicity during the Neonatal Intensive Care Unit Network Neurobehavioral Scale examination. They also had more nonoptimal reflexes and stress/abstinence signs compared with infants with prenatal exposure to cocaine only and those with prenatal exposure to alcohol, tobacco, and marijuana. CONCLUSION: Problems with arousal regulation were identified in infants with prenatal substance exposure. Autonomic dysregulation has been implicated as a mechanism by which these difficulties occur. Our results suggest that infants with prenatal exposure to both cocaine and opiates have the greatest autonomic response to the challenge of a sustained visual attention task, possibly putting these infants at risk for problems associated with physiologic and behavioral regulation, a necessary prerequisite for early learning.

Neurobehavioral disinhibition predicts initiation of substance use in children with prenatal cocaine exposure.

BACKGROUND: In previous work we (Fisher et al., 2011) examined the emergence of neurobehavioral disinhibition (ND) in adolescents with prenatal substance exposure. We computed ND factor scores at three age points (8/9, 11 and 13/14 years) and found that both prenatal substance exposure and early adversity predicted ND. The purpose of the current study was to determine the association between these ND scores and initiation of substance use between ages 8 and 16 in this cohort as early initiation of substance use has been related to later substance use disorders. Our hypothesis was that prenatal cocaine exposure predisposes the child to ND, which, in turn, is associated with initiation of substance use by age 16. METHODS: We studied 386 cocaine exposed and 517 unexposed children followed since birth in a longitudinal study. Five dichotomous variables were computed based on the subject's report of substance use: alcohol only; tobacco only; marijuana only; illicit substances and any substance. RESULTS: Cox proportional hazard regression showed that the 8/9 year ND score was related to initiation of alcohol, tobacco, illicit and any substance use but not marijuana use. The trajectory of ND across the three age periods was related to substance use initiation in all five substance use categories. Prenatal cocaine exposure, although initially related to tobacco, marijuana and illicit substance initiation, was no longer significant with ND scores in the models. CONCLUSION: Prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years portends substance use initiation.

Prenatal methamphetamine exposure and inhibitory control among young school-age children.

OBJECTIVE: To examine the association between prenatal methamphetamine exposure and inhibitory control in 66-month-old children followed since birth in the multicenter, longitudinal Infant Development, Environment, and Lifestyle study. STUDY DESIGN: The sample included 137 children with prenatal methamphetamine exposure and 130 comparison children matched for race, birth weight, maternal education, and type of insurance. Inhibitory control, an executive function related to emotional and cognitive control, was assessed using a computerized Stroop-like task developed for young children. Hierarchical linear modeling tested the relationship between the extent of prenatal methamphetamine exposure (heavy, some, or none) and accuracy and reaction time outcomes, adjusting for prenatal exposure to alcohol, tobacco, and marijuana; age; sex; socioeconomic status; caregiver IQ and psychological symptoms; Child Protective Services report of physical or sexual abuse; and site. RESULTS: In adjusted analyses, heavy prenatal methamphetamine exposure was related to reduced accuracy in both the incongruent and mixed conditions on the Stroop-like task. Caregiver psychological symptoms and Child Protective Services report of physical or sexual abuse were associated with reduced accuracy in the incongruent and mixed consitions and in the incongruent conditions, respectively. CONCLUSION: Heavy prenatal methamphetamine exposure, along with caregiver psychological distress and child maltreatment, are related to subtle deficits in inhibitory control during the early school-age years.

Prenatal methamphetamine exposure and childhood behavior problems at 3 and 5 years of age.

OBJECTIVE: We evaluated behavior problems in children who were prenatally exposed to methamphetamine (MA) at ages 3 and 5 years. METHODS: The Infant Development, Environment, and Lifestyle study, a prospective, longitudinal study of prenatal MA exposure and child outcome, enrolled subjects postpartum in Los Angeles, California; Honolulu, Hawaii; Des Moines, Iowa; and Tulsa, Oklahoma. Prenatal exposure was determined by maternal self-report and/or meconium results. Exposed and comparison groups were matched on race, birth weight, public health insurance, and education. Mothers in the comparison group denied use and had a negative meconium screen for amphetamines. Prenatal exposures to tobacco, alcohol, or marijuana occurred in both groups. At ages 3 and 5 years, 330 children (166 exposed and 164 comparison) were assessed for behavior problems by using the caregiver report on the Child Behavior Checklist. General linear mixed models were used to determine the effects of prenatal MA exposure, including heavy exposure (≥3 days per week), age, and the interaction of exposure and age on behavior problems with adjustment for other drugs of abuse and environmental risk factors. RESULTS: MA exposure was associated with increased emotional reactivity and anxious/depressed problems at both ages and externalizing and attention-deficit/hyperactivity disorder problems by age 5 years. Heavy exposure was related to attention problems and withdrawn behavior at both ages. There were no effects of MA on the internalizing or total behavior problems scales. CONCLUSIONS: This first report of behavior problems in patients as young as 3 years associated with MA exposure identifies an important public health problem. Continued follow-up can inform the development of preventive intervention programs.

Motor and cognitive outcomes through three years of age in children exposed to prenatal methamphetamine.

BACKGROUND: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. The impact of prenatal MA exposure on development in childhood is unknown. OBJECTIVE: To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age. DESIGN/METHODS: IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa OK, Des Moines IA, Los Angeles CA, and Honolulu HI). MA subjects (n=204) were identified by self report or GC/MS confirmation of amphetamine and metabolites in infant meconium. Comparison subjects (n=208) were matched (race, birth weight, maternal education, and type of insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, phencyclidine or cocaine only. The Peabody Developmental Motor Scales (PDMS-2) were administered to the infants at the 1 and 3 year visits. This analysis includes a subsample (n=350) of the IDEAL study with completed 1 and/or 3 year visits (n=330 and 281, respectively). At each annual visit we also conducted the Bayley Scales of Infant Development (BSID-II) as a general evaluation of mental and motor development. The BSID-II analysis includes a subsample (n=356) of the IDEAL study with completed 1, 2, and/or 3 year visits (n=331, 288, and 278 respectively). GLM analysis conducted on the PDMS-2 and BSID-II examined the effects of MA exposure and heavy MA exposure (≥3 days of use/week), with and without covariates. Longitudinal analyses were used to examine the effects of MA exposure on changes in motor and cognitive performance over time. RESULTS: Heavy MA exposure was associated with significantly lower grasping scores than some and no use at 1 year (P=0.018). In longitudinal analysis, lower grasping scores associated with any MA exposure and heavy exposure persisted to 3 years. There were no effects of MA exposure, including heavy exposure, on the Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) at any or across age. CONCLUSIONS: There were no differences in cognition as assessed by the BSID-II between the groups. There was a subtle MA exposure effect on fine motor performance at 1 year with the poorest performance observed in the most heavily exposed children. By 3 years, no differences in fine motor performance were observed. These findings suggest MA exposure has modest motor effects at 1 year that are mostly resolved by 3 years.

Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand.

BACKGROUND: Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants. DESIGN: The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte. RESULTS: MA exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress. CONCLUSION: Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress.

Sleep problems in children with prenatal substance exposure: the Maternal Lifestyle study.

OBJECTIVE: To examine the associations between sleep problems and prenatal exposure to cocaine, opiates, marijuana, alcohol, and nicotine in children aged 1 month to 12 years. DESIGN: Sleep data were collected by maternal report in a prospective longitudinal follow-up of children participating in the Maternal Lifestyle multisite study. SETTING: Hospital-based research centers in Providence, Rhode Island; Miami, Florida; Detroit, Michigan; and Memphis, Tennessee. PARTICIPANTS: There were 808 participants, 374 exposed to cocaine and/or opiates, and 434 comparison subjects. MAIN EXPOSURE: Prenatal cocaine, opiate, marijuana, alcohol, and/or nicotine exposure. OUTCOME MEASURE: Sleep problems in early, middle, and/or late childhood, assessed as composites of maternal report items. RESULTS: Of the 5 substances, prenatal nicotine exposure was the only unique predictor of sleep problems (B = 0.074, R(2) change = 0.008, P = .01), with adjustment for covariates, including socioeconomic status, marital status, physical abuse, prenatal medical care, and postnatal cigarette smoke exposure. CONCLUSIONS: Prenatal exposure to nicotine was positively associated with children's sleep problems persisting throughout the first 12 years of life. Targeting of this group of children for educational and behavioral efforts to prevent and treat sleep problems is merited given that good sleep may serve as a protective factor for other developmental outcomes.

Small for gestational age and higher birth weight predict childhood obesity in preterm infants.

We sought to determine the association between small for gestational age (SGA), birth weight, and childhood obesity within preterm polysubstance exposed children. We sampled 312 preterm children with 11-year body mass index (BMI; age- and sex-specific) data from the Maternal Lifestyle Study (51% girls, 21.5% SGA, 46% prenatal cocaine, and 55% tobacco exposed). Multinomial regression analyzed the association between 11-year obesity (OBE) and overweight (OW) and SGA, birth weight, first-year growth velocity, diet, and physical activity variables. Overall, 24% were OBE (BMI for age ≥95th percentile) and 16.7% were OW (BMI ≥85th and <95th percentiles). In adjusted analyses, SGA was associated with OW (odds ratio [OR] = 3.4, confidence interval [CI] 1.5 to 7.5). Higher birth weight was associated with OBE (OR = 1.8, CI 1.3 to 2.4) and OW (OR = 1.4, CI 1.1 to 2.0). Growth velocity was associated with OBE (OR = 2.7, CI 1.8 to 4.0) and OW (OR = 1.6, CI 1.1 to 2.4). Low exercise was associated with OBE (OR = 2.1, CI 1.0 to 4.4) and OW (OR = 2.1, CI 1.0 to 4.5). There was no effect of substance exposure on obesity outcomes. Many (41%) of these high-risk preterm 11-year-olds were obese/overweight. Multiple growth-related processes may be involved in obesity risk for preterm children, including fetal programming as indicated by the SGA effect.

Prenatal cocaine exposure related to cortisol stress reactivity in 11-year-old children.

OBJECTIVE: Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school-aged children. STUDY DESIGN: Subjects included 743 11-year-old children (n = 320 cocaine-exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse, and quality of the home. RESULTS: With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Children exposed to cocaine and who experienced domestic violence showed the strongest effects. CONCLUSIONS: The combination of prenatal cocaine exposure and an adverse postnatal environment could downregulate the hypothalamic-pituitary-adrenal axis resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease.

Patterns of methamphetamine use during pregnancy: results from the Infant Development, Environment, and Lifestyle (IDEAL) Study.

The objectives of this study are to characterize methamphetamine (MA) usage patterns during pregnancy, examine whether patterns of MA use are associated with sociodemographic characteristics and prenatal care, and test the hypothesis that persistent or increasing MA use during pregnancy is associated with greater use of other illicit drugs. The sample consisted of 191 MA-using mothers who participated in a large-scale multi-site study of prenatal MA exposure. Patterns of substance use were assessed by maternal self-report via the Substance Use Inventory (SUI), which included detailed information about MA use, including frequency, quantity, and maximum use during each trimester of pregnancy. The study demonstrated that on average, the prevalence of MA use decreased over the three trimesters of pregnancy (84.3% vs. 56.0% vs. 42.4%), and decreased frequency was observed among users from the first trimester to the third (3.1 vs. 2.4 vs. 1.5 days/week). Closer examination of the individual patterns revealed that 29.3% of women maintained consistently high frequency, 9.4% increased frequency, 25.7% had a stable low/moderate pattern, and 35.6% decreased their frequency of MA over the course of pregnancy. These four groups did not differ in sociodemographic characteristics; women who decreased their use of MA had significantly more prenatal visits compared to the consistently high-use group, but were the most likely to use alcohol during their pregnancy. In conclusion, this article elucidated the different patterns of MA use in this community sample. Approximately, one third of MA-using mothers could be classified as consistently high users with a profile of use with the greatest risk to themselves and potentially to their infants including high levels of MA use throughout pregnancy and fewer prenatal care visits. Overall, we found that MA use declined across pregnancy; however, a substantial proportion of users had consistently high or increasing MA use, while those who decreased their MA frequency had a higher prevalence of polydrug use. Future research will investigate the association of these patterns with neonatal outcomes.

Identification of prenatal amphetamines exposure by maternal interview and meconium toxicology in the Infant Development, Environment and Lifestyle (IDEAL) study.

The Infant Development Environment and Lifestyle study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration, and magnitude of maternal MAMP exposure affect qualitative and quantitative meconium results. Interviews regarding maternal drug use were collected shortly after birth; meconium specimens were screened for amphetamines, cannabis, and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry. The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) meconium results were confirmed by gas chromatography mass spectrometry. Tobacco exposure was equally detected by immunoassay cotinine screening and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use or frequency or route of MAMP use. Maternal self-report was more sensitive than meconium testing for identifying MAMP and cannabis-exposed neonates; however, the timing of drug exposure may influence meconium toxicology results. Most women stopped MAMP and cannabis use before the third trimester. In the first trimester, meconium has not yet formed, and based on our recent results for opiates and cocaine, drug use in the second trimester appears to be poorly reflected in meconium. Low confirmation rates in meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers.

Longitudinal study of maternal report of sleep problems in children with prenatal exposure to cocaine and other drugs.

Sleep data were collected by maternal report in a prospective longitudinal follow up of cocaine-exposed and unexposed children. There were 139 participants: 23 with no prenatal drug exposure, 55 exposed to cocaine alone or in combination with other drugs, and 61 exposed to drugs other than cocaine. Characteristics differed between exposure groups including birth size, caretaker changes, maternal socioeconomic status, and postnatal drug use. Compared to those with no drug exposure, children with prenatal drug exposure other than cocaine experienced greater sleep problems (p = .026). Prenatal nicotine exposure was a unique predictor of sleep problems (p = .048). Early sleep problems predicted later sleep problems (all ps < .01). Together, these preliminary findings suggest possible neurotoxic sleep effects that persist over time. Larger studies, however, need to be conducted that better control for potential postnatal confounding factors.

Maternal smoking during pregnancy and newborn neurobehavior: effects at 10 to 27 days.

OBJECTIVE: To examine effects of maternal smoking during pregnancy on newborn neurobehavior at 10 to 27 days. STUDY DESIGN: Participants were 56 healthy infants (28 smoking-exposed, 28 unexposed) matched on maternal social class, age, and alcohol use. Maternal smoking during pregnancy was determined by maternal interview and maternal saliva cotinine. Postnatal smoke exposure was quantified by infant saliva cotinine. Infant neurobehavior was assessed through the NICU Network Neurobehavioral Scale. RESULTS: Smoking-exposed infants showed greater need for handling and worse self-regulation (P < .05) and trended toward greater excitability and arousal (P < .10) relative to matched, unexposed infants (all moderate effect sizes). In contrast to prior studies of days 0 to 5, no effects of smoking-exposure on signs of stress/abstinence or muscle tone emerged. In stratified, adjusted analyses, only effects on need for handling remained significant (P < .05, large effect size). CONCLUSIONS: Effects of maternal smoking during pregnancy at 10 to 27 days are subtle and consistent with increased need for external intervention and poorer self-regulation. Along with parenting deficits, these effects may represent early precursors for long-term adverse outcomes from maternal smoking during pregnancy. That signs of abstinence shown in prior studies of 0- to 5-day-old newborns did not emerge in older newborns provides further evidence for the possibility of a withdrawal process in exposed infants.

Prenatal methamphetamine use and neonatal neurobehavioral outcome.

BACKGROUND: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How prenatal MA exposure affects neonatal neurobehavior is unknown. OBJECTIVE: To examine the neurobehavioral effects of prenatal MA exposure. DESIGN: The Infant Development, Environment and Lifestyle (IDEAL) study screened 13,808 subjects and 1632 were eligible and consented. 166 (n=74 exposed) were enrolled in a longitudinal follow-up. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life. Analyses conducted on NNNS summary scores included exposure group effects, heavy MA use effects, association with frequency of use by trimester, and dose-response relationships with amphetamine metabolites. RESULTS: After adjusting for covariates, exposure to MA was associated with increased physiological stress. Heavy MA use was related to lower arousal, more lethargy, and increased physiological stress. First trimester MA use was related to elevated stress abstinence. Third trimester use was related to poorer quality of movement. Higher level of amphetamine metabolites in meconium was associated with increased CNS stress. CONCLUSIONS: Prenatal MA exposure was associated with neurobehavioral patterns of decreased arousal, increased stress, and poor quality of movement. The dose-response relationships may represent neurotoxic effects from MA.

The infant development, environment, and lifestyle study: effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth.

OBJECTIVE: Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development, Environment and Lifestyle study. DESIGN/METHOD: The Infant Development, Environment and Lifestyle study screened 13808 subjects at 4 clinical centers: 1618 were eligible and consented, among which 84 were methamphetamine exposed, and 1534 were unexposed. Those who were methamphetamine exposed were identified by self-report and/or gas chromatography-mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Those who were unexposed denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, or marijuana use, but excluded use of opiates, LSD, PCP or cocaine only. Neonatal parameters included birth weight and gestational age in weeks. One-way analysis of variance and linear-regression analyses were conducted on birth weight by exposure. The relationship of methamphetamine exposure and the incidence of small for gestational age was analyzed using multivariate logistic-regression analyses. RESULTS: The methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly 2 times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birthweight in the methamphetamine exposed group was lower than the unexposed group. CONCLUSIONS: These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth abnormalities in the future.

Methamphetamine and other substance use during pregnancy: preliminary estimates from the Infant Development, Environment, and Lifestyle (IDEAL) study.

OBJECTIVES: Methamphetamine use is a continuing problem in several regions of the United States and yet few studies have focused on prenatal methamphetamine exposure. The purpose of this study was to estimate the prevalence and correlates of alcohol, tobacco, and other substance use-including methamphetamine-during pregnancy. METHODS: The sample consisted of the first 1632 eligible mothers who consented to participate in a large-scale multisite study focused on prenatal methamphetamine exposure. This unselected screening sample included both users and nonusers of alcohol, tobacco, methamphetamine, and other drugs. Substance use was determined by maternal self-report and/or GC/MS confirmation of a positive meconium screen. RESULTS: Overall, 5.2% of women used methamphetamine at some point during their pregnancy. One quarter of the sample smoked tobacco, 22.8% drank alcohol, 6.0% used marijuana, and 1.3% used barbiturates prenatally. Less than 1% of the sample used heroin, benzodiazepines, and hallucinogens. Multivariate modeling results showed that tobacco smokers and illicit drug users were more likely to be single and less educated, have attended less than 11 prenatal visits, and utilize public financial assistance. CONCLUSIONS: This is the first large-scale investigation to report the prevalence of methamphetamine use during pregnancy in areas of the United States where methamphetamine is a notable concern. Follow-up research is ongoing to investigate the outcomes associated with prenatal methamphetamine exposure. Given that this research extends and confirms previous findings showing that high-risk groups of pregnant women can be identified on the basis of basic demographic characteristics, targeted interventions are greatly needed to reduce serious adverse outcomes associated with prenatal alcohol and tobacco use.