Fisher, Philip A. | Lester, Barry M. | DeGarmo, David S. | LaGasse, Linda L. | Lin, Hai | Shankaran, Seetha | Bada, Henrietta S. | Bauer, Charles R. | Hammond, Jane | Whitaker, Toni | Higgins, Rosemary
The negative effects of prenatal substance exposure on neurobiological and psychological development and of early adversity are clear, but little is known about their combined effects. In this study, multilevel analyses of the effects of prenatal substance exposure and early adversity on the emergence of neurobehavioral disinhibition in adolescence were conducted. Neurobehavioral disinhibition has previously been observed to occur frequently in multiproblem youth from high-risk backgrounds. In the present study, neurobehavioral disinhibition was assessed via behavioral dysregulation and poor executive function composite measures. Data were drawn from a prospective longitudinal investigation of prenatal substance exposure that included 1073 participants followed from birth through adolescence. The results from latent growth modeling analyses showed mean stability but significant individual differences in behavioral dysregulation and mean decline with individual differences in executive function difficulties. Prior behavioral dysregulation predicted increased executive function difficulties. Prenatal drug use predicted the emergence and growth in neurobehavioral disinhibition across adolescence (directly for behavioral dysregulation and indirectly for executive function difficulties via early adversity and behavioral dysregulation). Prenatal drug use and early adversity exhibited unique effects on growth in behavioral dysregulation; early adversity uniquely predicted executive function difficulties. These results are discussed in terms of implications for theory development, social policy, and prevention science.
doi:10.1017/S0954579411000290
PMCID: PMC3335443
PMID: 21756431
LaGasse, Linda L. | Gaskins, Ronnesia B. | Bada, Henrietta S. | Shankaran, Seetha | Liu, Jing | Lester, Barry M. | Bauer, Charles R. | Higgins, Rosemary D. | Das, Abhik | Roberts, Mary
Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI] ≥ 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcohol were 4 times more likely to be obese (OR 4.11, CI 2.04–9.76) than children not exposed to either drug. No increase in obesity prevalence was found in children exposed to alcohol but not cocaine (OR 1.08, CI .59–1.93) or both (OR 1.21, CI 0.66–2.22). Alcohol exposure may attenuate the effect of cocaine exposure on obesity. Increased obesity associated with cocaine but not alcohol exposure was first observed at 7 years. BMI was also elevated from 3 to 9 years in children exposed to cocaine but not alcohol, due to increasing weight but normal height. Prenatal exposure to cocaine may alter the neuroendocrine system and metabolic processes resulting in increased weight gain and childhood obesity.
doi:10.1016/j.ntt.2010.11.002
PMCID: PMC3058125
PMID: 21109003
Prenatal cocaine exposure; prenatal alcohol exposure; childhood obesity; growth; fetal origins
LaGasse, Linda L. | Wouldes, Trecia | Newman, Elana | Smith, Lynne M. | Shah, Rizwan Z. | Derauf, Chris | Huestis, Marilyn A. | Arria, Amelia M. | Grotta, Sheri Della | Wilcox, Tara | Lester, Barry M.
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.
doi:10.1016/j.ntt.2010.06.009
PMCID: PMC2974956
PMID: 20615464
Prenatal exposure; Methamphetamine; Neurodevelopment; Meconium
Smith, Lynne M. | LaGasse, Linda L. | Derauf, Chris | Newman, Elana | Shah, Rizwan | Haning, William | Arria, Amelia | Huestis, Marilyn | Strauss, Arthur | Grotta, Sheri Della | Dansereau, Lynne M. | Lin, Hai | Lester, Barry M.
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, 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.
doi:10.1016/j.ntt.2010.10.004
PMCID: PMC3033584
PMID: 21256431
prenatal exposure; neurodevelopment; Bayley; Peabody
Nguyen, Diana | Smith, Lynne M. | LaGasse, Linda L. | Derauf, Chris | Grant, Penny | Shah, Rizwan | Arria, Amelia | Huestis, Marilyn A. | Haning, William | Strauss, Arthur | Grotta, Sheri Della | Liu, Jing | Lester, Barry M. | AJ | WFB
Previous studies suggest prenatal methamphetamine (MA) exposure inhibits fetal growth. We examined neonatal growth effects of prenatal MA exposure in a prospective cohort study. After adjusting for covariates, exposed neonates had a higher incidence of being small for gestational age (SGA) than unexposed neonates.
doi:10.1016/j.jpeds.2010.04.024
PMCID: PMC3018351
PMID: 20570284
drug; amphetamine; antenatal; small for gestational age
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. Cocaine exposed children exposed to domestic violence showed the strongest effects.
Conclusion
The combination of prenatal cocaine exposure and an adverse postnatal environment could down regulate the hypothalamic-pituitary-adrenal axis (HPA) resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease.
doi:10.1016/j.jpeds.2010.02.039
PMCID: PMC3121327
PMID: 20400094
prenatal cocaine exposure; cortisol reactivity; environmental adversity
Della Grotta, Sheri | LaGasse, Linda L. | Arria, Amelia M. | Derauf, Chris | Grant, Penny | Smith, Lynne M. | Shah, Rizwan | Huestis, Marilyn | Liu, Jing | Lester, Barry M.
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 demostrated 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.
doi:10.1007/s10995-009-0491-0
PMCID: PMC2895902
PMID: 19565330
Methamphetamine; Pregnancy; Alcohol and other drug use; Women; Epidemiology
Gray, Teresa R. | Kelly, Tamsin | LaGasse, Linda L. | Smith, Lynne M. | Derauf, Chris | Grant, Penny | Shah, Rizwan | Arria, Amelia | Haning, William | Grotta, Sheri Della | Strauss, Arthur | Lester, Barry M. | Huestis, Marilyn A.
BACKGROUND
Prenatal methamphetamine (MAMP) exposure is poorly reflected in neonatal meconium. Often, maternal self-reported MAMP use is not corroborated by positive results in amphetamines immunoassays of meconium, and even if initial test results are positive, they frequently are not confirmed for MAMP or amphetamine (AMP) by chromatographic analysis. The presence of the MAMP metabolites p-hydroxymethamphetamine (pOHMAMP), p-hydroxyamphetamine (pOHAMP), and norephedrine (NOREPH) in meconium may improve the identification of MAMP- and AMP-exposed neonates.
METHODS
Immunoassay-positive and -negative meconium samples were subjected to liquid chromatography–tandem mass spectrometric reanalysis for these recently identified metabolites.
RESULTS
pOHAMP and NOREPH were detected only when MAMP and/or AMP were present and thus do not appear to be promising biomarkers of prenatal MAMP exposure. pOHMAMP, in contrast, identified 6 additional neonates whose mothers reported MAMP exposure, yet had a meconium sample screened as negative; pOHMAMP was more likely to be present if maternal MAMP use continued into the third trimester. Although the pOHMAMP results for meconium samples corroborated the maternal self-reports, the confirmation rate for positive meconium screening results did not improve with the inclusion of these new biomarkers.
CONCLUSIONS
pOHMAMP identified additional MAMP-exposed neonates; therefore, MAMP, AMP, and pOHMAMP should be included in meconium chromatographic analyses. To maximize the identification of MAMP-exposed children requires improvement in immunoassay screening tests to reduce false-negative and false-positive results. Additional research will help clarify which AMP-related compounds, if any, contribute to unconfirmed positive results in screening tests. Furthermore, nonamphetamine compounds endogenous to the complex meconium matrix also may cross-react, making chromatographic confirmation of screening results essential.
doi:10.1373/clinchem.2009.139055
PMCID: PMC2883877
PMID: 20185623
Objective
To examine the relationships between sleep problems and prenatal exposure to cocaine, opiates, marijuana, alcohol, and nicotine in children 1 month to 12 years of age.
Design
Sleep data was 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, RI, Miami, FL, Detroit, MI, and Memphis, TN
Participants
There were 808 participants: 374 exposed to cocaine and/or opiates; 434 comparison.
Main exposure
Prenatal cocaine, opiate, marijuana, alcohol, and nicotine exposure.
Outcome measure
Sleep problems in early, middle, and late childhood, assessed as composites of maternal report items.
Results
Of the five substances, prenatal nicotine exposure was the only unique predictor of sleep problems (B = .074, R2 Δ = .008, p = .012) with adjustment for covariates including SES, marital status, physical abuse, prenatal medical care, and postnatal cigarette smoke exposure.
Conclusion
Prenatal exposure to nicotine was positively associated with children's sleep problems persisting throughout the first 12 years of life. Targeting 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.
doi:10.1001/archpediatrics.2010.52
PMCID: PMC2917192
PMID: 20439796
Gaskins, Ronnesia B. | LaGasse, Linda L. | Liu, Jing | Shankaran, Seetha | Lester, Barry M. | Bada, Henrietta S. | Bauer, Charles R. | Das, Abhik | Higgins, Rosemary D. | Roberts, Mary
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.
doi:10.1055/s-0030-1253555
PMCID: PMC2949419
PMID: 20408111
Childhood obesity; premature birth; infant SGA; birth weight; exercise; prenatal drug exposure
Objective
To examine effects of maternal smoking during pregnancy on newborn neurobehavior at 10–27 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 0–5, 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 10–27 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 0–5 day-old newborns did not emerge in older newborns provides further evidence for the possibility of a withdrawal process in exposed infants.
doi:10.1016/j.jpeds.2008.07.048
PMCID: PMC3026585
PMID: 18990408
maternal smoking; newborn; infant; behavior; NNNS; cotinine; pregnancy
Gray, Teresa R. | LaGasse, Linda L. | Smith, Lynne M. | Derauf, Chris | Grant, Penny | Shah, Rizwan | Arria, Amelia M. | Della Grotta, Sheri A. | Strauss, Arthur | Haning, William F. | Lester, Barry M. | Huestis, Marilyn A.
The Infant Development Environment and Lifestyle (IDEAL) 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.
Materials and Methods
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 (GCMS).
Results
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 GCMS. Tobacco exposure was equally detected by immunoassay cotinine screen and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use, frequency or route of MAMP use.
Discussion
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 ceased 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.
Conclusion
Low confirmation rates in meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers.
doi:10.1097/FTD.0b013e3181bb438e
PMCID: PMC2784609
PMID: 19935364
methamphetamine; pregnancy; meconium; in utero; cannabis; tobacco; prenatal drug exposure; amphetamines
Lester, Barry M. | Bagner, Daniel M. | Liu, Jing | LaGasse, Linda L. | Seifer, Ronald | Bauer, Charles R. | Shankaran, Seetha | Bada, Henrietta | Higgins, Rosemary D. | Das, Abhik
OBJECTIVE
To test a developmental model of neurobehavioral dysregulation relating prenatal substance exposure to behavior problems at age 7.
PATIENTS AND METHODS
The sample included 360 cocaine-exposed and 480 unexposed children from lower to lower middle class families of which 78% were African American. Structural equation modeling (SEM) was used to test models whereby prenatal exposure to cocaine and other substances would result in neurobehavioral dysregulation in infancy, which would predict externalizing and internalizing behavior problems in early childhood. SEM models were developed for individual and combined parent and teacher report for externalizing, internalizing, and total problem scores on the Child Behavior Checklist.
RESULTS
The Goodness of Fit Statistics indicated that all of the models met criteria for adequate fit with 7 of the 9 models explaining 18 to 60% of the variance in behavior problems at age 7. The paths in the models indicate that there are direct effects of prenatal substance exposure on 7-year behavior problems as well as indirect effects, including neurobehavioral dysregulation.
CONCLUSIONS
Prenatal substance exposure affects behavior problems at age 7 through two mechanisms. The direct pathway is consistent with a teratogenic effect. Indirect pathways suggest cascading effects where prenatal substance exposure results in neurobehavioral dysregulation manifesting as deviations in later behavioral expression. Developmental models provide an understanding of pathways that describe how prenatal substance exposure affects child outcome and have significant implications for early identification and prevention.
doi:10.1542/peds.2008-2898
PMCID: PMC2874881
PMID: 19822596
Prenatal substance exposure; cocaine; neurobehavioral dysregulation; behavior problems
Paz, Monica S. | Smith, Lynne M. | LaGasse, Linda L. | Derauf, Chris | Grant, Penny | Shah, Rizwan | Arria, Amelia | Huestis, Marilyn | Haning, William | Strauss, Arthur | Grotta, Sheri Della | Liu, Jing | Lester, Barry M.
Background
The effects of maternal depression on neonatal neurodevelopment in MA exposed neonates have not been well characterized.
Objective
To determine the neurobehavioral effects of maternal depressive symptoms on neonates exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS).
Design
The purpose of the IDEAL study is to determine the effects of prenatal MA exposure on child outcome. IDEAL screened 13,808 subjects, 1632 were eligible and consented and 176 mothers were enrolled. Only biological mothers with custody of their child at the one-month visit (n=50 MA; n=86 comparison) had the Addiction Severity Index (ASI) administered. The NNNS was administered to the neonate by an examiner blinded to MA exposure within the first five days of life. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS outcomes, with and without covariates. Significance was accepted at p<.05.
Results
After adjusting for covariates, regardless of exposure status, maternal depressive symptoms were associated with lower handling and arousal scores, elevated physiological stress scores and an increased incidence of hypotonicity. When adjusting for covariates, MA exposure was associated with lower arousal and higher lethargy scores.
Conclusions
Maternal depressive symptoms are associated with neurodevelopmental patterns of decreased arousal and increased stress. Prenatal MA exposure combined with maternal depression was not associated with any additional neonatal neurodevelopmental differences.
doi:10.1016/j.ntt.2008.11.004
PMCID: PMC2684459
PMID: 19059478
Prenatal exposure; Neurodevelopment; Drugs; Depression
Bagner, Daniel M. | Sheinkopf, Stephen J. | Miller-Loncar, Cynthia | LaGasse, Linda L. | Lester, Barry M. | Liu, Jing | Bauer, Charles R. | Shankaran, Seetha | Bada, Henrietta | Das, Abhik
Objective
To examine the relationship between early parenting stress and later child behavior in a high risk sample and measure the effect of drug exposure on the relationship between parenting stress and child behavior.
Methods
A subset of child-caregiver dyads (n = 607) were selected from the Maternal Lifestyle Study, which is a large sample of children (n = 1388) with prenatal cocaine exposure and a comparison sample unexposed to cocaine. Of the 607 dyads, 221 were prenatally exposed to cocaine and 386 were unexposed to cocaine. Selection was based on the presence of a stable caregiver at 4 and 36 months with no evidence of change in caregiver between those time points.
Results
Parenting stress at 4 months significantly predicted child externalizing behavior at 36 months. These relations were unaffected by cocaine exposure suggesting the relationship between parenting stress and behavioral outcome exists for high-risk children regardless of drug exposure history.
Conclusions
These results extend the findings of the relationship between parenting stress and child behavior to a sample of high-risk children with prenatal drug exposure. Implications for outcome and treatment are discussed.
doi:10.1007/s10578-008-0109-6
PMCID: PMC2861499
PMID: 18626768
disruptive behavior; parenting stress; high-risk children; prenatal drug exposure; cocaine
Gray, Teresa R. | Kelly, Tamsin | LaGasse, Linda L. | Smith, Lynne M. | Derauf, Chris | Haning, William | Grant, Penny | Shah, Rizwan | Arria, Amelia | Strauss, Arthur | Lester, Barry M. | Huestis, Marilyn A.
Meconium analysis can detect fetal exposure to drugs taken by the mother during pregnancy. Methamphetamine and amphetamine have previously been observed in meconium of methamphetamine-exposed neonates; the presence of other metabolites has not been investigated. Detection of such analytes may lead to more sensitive identification and, thus improved medical treatment of affected infants.
Methods and Materials
Forty-three methamphetamine-positive meconium specimens were analyzed for newly identified methamphetamine biomarkers, p-hydroxymethamphetamine, p-hydroxyamphetamine, and norephedrine. Due to methamphetamine adulteration in illicit ecstasy and to simultaneously monitor 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine prenatal exposure, MDMA, its metabolites and related sympathomimetic amines were assayed.
Results
Methamphetamine, amphetamine and unconjugated p-hydroxymethamphetamine were the most prevalent and abundant analytes present in meconium; however, unconjugated p-hydroxyamphetamine and norephedrine also were identified.
Discussion
It is possible that one of these additional analytes could be important for predicting toxicity or maternal or neonatal outcome measures in fetuses exposed to methamphetamine at specific gestational ages or with different metabolic capabilities. Although these new biomarkers were present in lower concentrations than methamphetamine and amphetamine in the meconium of previously confirmed specimens, additional research will determine if inclusion of these analytes can increase identification of methamphetamine-exposed neonates.
Conclusion
Novel methamphetamine biomarker concentrations were characterized in meconium of infants exposed in utero to methamphetamine.
doi:10.1097/FTD.0b013e318195d7cb
PMCID: PMC2629503
PMID: 19125148
methamphetamine; meconium; in utero
Sleep data were collected by maternal report in a prospective longitudinal follow-up of cocaine exposed and unexposed children. There were 139 subjects: 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, and maternal SES and postnatal drug use. Compared to those with no drug exposure, children with prenatal drug exposure other than cocaine experienced greater sleep problems (mean [SD], 5 [4.93] vs 7.7 [4.85], p = .026). Prenatal nicotine exposure was a unique predictor of sleep problems (R2 = .028, p = .048). Early sleep problems predicted later sleep problems (all p’s <.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.
doi:10.1080/15402000903190108
PMCID: PMC2766926
PMID: 19787489
Derauf, Chris | LaGasse, Linda L. | Smith, Lynne M. | Grant, Penny | Shah, Rizwan | Arria, Amelia | Huestis, Marilyn | Haning, William | Strauss, Arthur | Grotta, Sheri Della | Liu, Jing | Lester, Barry M.
This study describes the psychological characteristics and caretaking environments of 131 women enrolled in the first longitudinal study of prenatal methamphetamine (MA) exposure and child development. Prenatal MA use was associated with lower maternal perceptions on quality of life, greater likelihood of substance use among family and friends, increased risk for ongoing legal difficulties, and a markedly increased likelihood of developing a substance abuse disorder. Our preliminary findings suggest that MA using women are more likely to have multiple, intertwined psychosocial risks that may result in maladaptive parenting and caregiving. These factors may impact the developmental outcomes of affected children.
doi:10.1080/00952990601175029
PMCID: PMC2737408
PMID: 17497551
Maternal behavior; methamphetamine; parenting; substance abuse
Della Grotta, Sheri | LaGasse, Linda L. | Arria, Amelia M. | Derauf, Chris | Grant, Penny | Smith, Lynne M. | Shah, Rizwan | Huestis, Marilyn | Liu, Jing | Lester, Barry M.
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 demostrated 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.
doi:10.1007/s10995-009-0491-0
PMCID: PMC2895902
PMID: 19565330
Methamphetamine; Pregnancy; Alcohol and other drug use; Women; Epidemiology
This study investigated the potential long-term effects of cocaine exposure on brain functioning using fMRI in school-aged children. The sample included 12 children with prenatal cocaine exposure and 12 non-exposed children (8–9 years old). Groups did not differ on IQ, socioeconomic status, or perinatal risk factors. A response inhibition task was administered during an fMRI scan using a 1.5-T MRI system. Task performance did not differentiate groups, but groups were differentiated by patterns of task-related brain activity. Cocaine-exposed children showed greater activation in the right inferior frontal cortex and caudate during response inhibition, whereas non-exposed children showed greater activations in temporal and occipital regions. These preliminary findings suggest that prenatal cocaine may affect the development of brain systems involved in the regulation of attention and response inhibition.
doi:10.1159/000207503
PMCID: PMC2951722
PMID: 19372696
Prenatal cocaine; Neuroimaging; Cognitive development; Inhibition
Smith, Lynne M. | LaGasse, Linda L. | Derauf, Chris | Grant, Penny | Shah, Rizwan | Arria, Amelia | Huestis, Marilyn | Haning, William | Strauss, Arthur | Grotta, Sheri Della | Fallone, Melissa | LiuPhD, Jing | Lester, Barry M.
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 physiological stress. 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.
doi:10.1016/j.ntt.2007.09.005
PMCID: PMC2358984
PMID: 18031987
prenatal exposure; neurodevelopment; drug; meconium