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1.  Infant Neurobehavioral Development 
Seminars in perinatology  2011;35(1):8-19.
The trend toward single-room neonatal intensive care units (NICUs) is increasing; however scientific evidence is, at this point, mostly anecdotal. This is a critical time to assess the impact of the single-room NICU on improving medical and neurobehavioral outcomes of the preterm infant. We have developed a theoretical model that may be useful in studying how the change from an open-bay NICU to a single-room NICU could affect infant medical and neurobehavioral outcome. The model identifies mediating factors that are likely to accompany the change to a single-room NICU. These mediating factors include family centered care, developmental care, parenting and family factors, staff behavior and attitudes, and medical practices. Medical outcomes that plan to be measured are sepsis, length of stay, gestational age at discharge, weight gain, illness severity, gestational age at enteral feeding, and necrotizing enterocolitis (NEC). Neurobehavioral outcomes include the NICU Network Neurobehavioral Scale (NNNS) scores, sleep state organization and sleep physiology, infant mother feeding interaction scores, and pain scores. Preliminary findings on the sample of 150 patients in the open-bay NICU showed a “baseline” of effects of family centered care, developmental care, parent satisfaction, maternal depression, and parenting stress on the neurobehavioral outcomes of the newborn. The single-room NICU has the potential to improve the neurobehavioral status of the infant at discharge. Neurobehavioral assessment can assist with early detection and therefore preventative intervention to maximize developmental outcome. We also present an epigenetic model of the potential effects of maternal care on improving infant neurobehavioral status.
doi:10.1053/j.semperi.2010.10.003
PMCID: PMC3168949  PMID: 21255702
preterm; neurobehavior; NNNS; NICU; very-low-birthweight infants; single-room NICU design; epigenetics
2.  Atypical Cry Acoustics in 6-Month-Old Infants at Risk for Autism Spectrum Disorder 
This study examined differences in acoustic characteristics of infant cries in a sample of babies at risk for autism and a low-risk comparison group. Cry samples derived from vocal recordings of 6-month-old infants at risk for autism spectrum disorder (ASD; n = 21) and low-risk infants (n = 18) were subjected to acoustic analyses using analysis software designed for this purpose. Cries were categorized as either pain-related or non-pain-related based on videotape coding. At-risk infants produced pain-related cries with higher and more variable fundamental frequency (F0) than low-risk infants. At-risk infants later classified with ASD at 36 months had among the highest F0 values for both types of cries and produced cries that were more poorly phonated than those of nonautistic infants, reflecting cries that were less likely to be produced in a voiced mode. These results provide preliminary evidence that disruptions in cry acoustics may be part of an atypical vocal signature of autism in early life.
doi:10.1002/aur.1244
PMCID: PMC3517274  PMID: 22890558
autism; infancy; cry; vocalizations; acoustic analysis
3.  Newborn neurobehavioral patterns are differentially related to prenatal maternal Major Depressive Disorder and Serotonin Reuptake Inhibitor treatment 
Depression and Anxiety  2011;28(11):1008-1019.
Background
Prenatal serotonin reuptake inhibitor (SRI) exposure has been related to adverse newborn neurobehavioral outcomes; however these effects have not been compared to those that may arise from prenatal exposure to maternal major depressive disorder (MDD) without SRI treatment. This study examined potential effects of MDD with and without SRI treatment on newborn neurobehavior.
Methods
This was a prospective, naturalistic study. Women were seen at an outpatient research center twice during pregnancy (26–28 and 36–38 weeks gestational age (GA)). Psychiatric diagnoses were assessed using the Structured Clinical Interview for the DSM-IV; medication use was measured with the Timeline Follow-Back instrument. Three groups were established based upon MDD diagnosis and SRI use: Control (N=56), MDD (N=20) or MDD+SRI (N=36). Infants were assessed on a single occasion within 3 weeks of birth with the NICU Network Neurobehavioral Assessment Scale (NNNS). Generalized Linear Modeling was used to examine neurobehavioral outcomes by exposure group and infant age at assessment.
Results
Full-term infants exposed to MDD+SRIs had a lower GA than CON or MDD-exposed infants and, controlling for GA, had lower quality of movement and more central nervous system stress signs. In contrast, MDD-exposed infants had the highest quality of movement scores, while having lower attention scores than CON and MDD+SRI-exposed infants.
Conclusion
MDD+SRI-exposed infants appear to have a different neurobehavioral profile than MDD-exposed infants in the first three weeks after delivery; both groups may have different neurobehavioral profiles with increasing age from birth.
doi:10.1002/da.20883
PMCID: PMC3215845  PMID: 21898709
infant; motor quality; central nervous system; depression; pregnancy; treatment
4.  Prenatal Cocaine Exposure and Small-for-Gestational-Age Status: Effects on Growth at 6 Years of age 
Neurotoxicology and teratology  2011;33(5):575-581.
OBJECTIVE
To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.
STUDY DESIGN
Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.
RESULTS
At birth cocaine-exposed infants (n=364) had significantly lower growth parameters compared to non-exposed children (n=771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).
CONCLUSIONS
Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.
doi:10.1016/j.ntt.2011.04.003
PMCID: PMC3183411  PMID: 21849244
Prenatal cocaine exposure; small for gestational age; childhood growth
5.  The Combined Effects of Prenatal Drug Exposure and Early Adversity on Neurobehavioral Disinhibition in Childhood and Adolescence 
Development and Psychopathology  2011;23(3):777-788.
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
6.  Serial Pediatric Symptom Checklist Screening in Children with Prenatal Drug Exposure 
Objective
To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure.
Method
The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared to an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1,081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled.
Results
Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco pre- and post-natally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes.
Conclusion
Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group.
doi:10.1097/DBP.0b013e318208ee3c
PMCID: PMC3069136  PMID: 21200328
Behavior disorder; child behavior; mental health; screening; prenatal cocaine exposure; Pediatric Symptom Checklist
7.  Placental 11-Beta Hydroxysteroid Dehydrogenase Methylation Is Associated with Newborn Growth and a Measure of Neurobehavioral Outcome 
PLoS ONE  2012;7(3):e33794.
Background
There is growing evidence that the intrauterine environment can impact the neurodevelopment of the fetus through alterations in the functional epigenome of the placenta. In the placenta, the HSD11B2 gene encoding the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol, is regulated by DNA methylation, and has been shown to be susceptible to stressors from the maternal environment.
Methodology/Principal Findings
We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 185 healthy newborn infants and infant and maternal characteristics, as well as the association between this epigenetic variability and newborn neurobehavioral outcome assessed with the NICU Network Neurobehavioral Scales. Controlling for confounders, HSD11B2 methylation extent is greatest in infants with the lowest birthweights (P = 0.04), and this increasing methylation was associated with reduced scores of quality of movement (P = 0.04).
Conclusions/Significance
These results suggest that factors in the intrauterine environment which contribute to birth outcome may be associated with placental methylation of the HSD11B2 gene and that this epigenetic alteration is in turn associated with a prospectively predictive early neurobehavioral outcome, suggesting in some part a mechanism for the developmental origins of infant neurological health.
doi:10.1371/journal.pone.0033794
PMCID: PMC3303854  PMID: 22432047
8.  Prenatal Cocaine Exposure and Childhood Obesity at Nine Years 
Neurotoxicology and teratology  2010;33(2):188-197.
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
9.  Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand 
Neurotoxicology and teratology  2010;33(1):166-175.
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
10.  Intrauterine Growth of Infants Exposed to Prenatal Methamphetamine: Results from the Infant Development, Environment, and Lifestyle (IDEAL) Study 
The Journal of pediatrics  2010;157(2):337-339.
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
11.  Prenatal Cocaine Exposure Alters Cortisol Stress Reactivity in 11 Year Old Children 
The Journal of pediatrics  2010;157(2):288-295.e1.
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
12.  New Meconium Biomarkers of Prenatal Methamphetamine Exposure Increase Identification of Affected Neonates 
Clinical chemistry  2010;56(5):856-860.
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
13.  The Maternal Lifestyle Study: Sleep Problems in Children with Prenatal Substance Exposure 
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
14.  Small for Gestational Age and Higher Birth Weight Predict Childhood Obesity in Preterm Infants 
American journal of perinatology  2010;27(9):721-730.
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
15.  Identification of Prenatal Amphetamines Exposure by Maternal Interview and Meconium Toxicology in the Infant Development, Environment and Lifestyle (IDEAL) Study 
Therapeutic drug monitoring  2009;31(6):769-775.
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
16.  Infant Neurobehavioral Dysregulation Related to Behavior Problems in Children with Prenatal Substance Exposure 
Pediatrics  2009;124(5):1355-1362.
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
17.  A Preliminary Study of Cortisol Reactivity and Behavior Problems in Young Children Born Premature 
Developmental psychobiology  2010;52(6):574-582.
The purpose of the present study was to examine the relation between cortisol reactivity and comorbid internalizing and externalizing behavior problems among children born premature. Children between the ages of 18 and 60 months who were born < 37 weeks gestation and presented with clinically significant externalizing behavior problems were included. Children were categorized based on those who mounted a cortisol response to a stressor and those who did not mount a cortisol response. Children demonstrating the cortisol response were reported to have more problems with attention, emotional reactivity, anxiety, and depression based on maternal report and displayed higher rates of negative verbalizations during a mother-child interaction than children without a cortisol response. These results extend the findings of the relation between cortisol reactivity and comorbid internalizing and externalizing behavior problems to a sample of children born premature.
doi:10.1002/dev.20464
PMCID: PMC2933079  PMID: 20806330
cortisol; prematurity; behavior problems; stress; assessment
18.  Fetal Effects of Psychoactive Drugs 
Clinics in perinatology  2009;36(3):595-619.
doi:10.1016/j.clp.2009.06.002
PMCID: PMC2767264  PMID: 19732616
cocaine; methamphetamine; SSRI; maternal depression; fetal behavior
19.  Services used by perinatal substance-users with child welfare involvement: a descriptive study 
Background
Substance use during pregnancy often leads to involvement in the child welfare system, resulting in multiple social service systems and service providers working with families to achieve successful child welfare outcomes. The Vulnerable Infants Program of Rhode Island (VIP-RI) is a care coordination program developed to work with perinatal substance-users to optimize opportunities for reunification and promote permanency for substance-exposed infants. This paper describes services used by VIP-RI participants and child welfare outcomes.
Methods
Data collected during the first four years of VIP-RI were used to identify characteristics of program participants, services received, and child welfare outcomes: closed child welfare cases, reunification with biological mothers and identified infant permanent placements.
Descriptive Results
Medical and financial services were associated with positive child welfare outcomes. Medical services included family planning, pre- and post-natal care and HIV test counseling. Financial services included assistance with obtaining entitlement benefits and receiving tangible support such as food and clothing.
Conclusions
Findings from this study suggest services that address basic family needs were related to positive child welfare outcomes. The provision of basic services, such as health care and financial assistance through entitlement benefits and tangible donations, may help to establish a foundation so mothers can concentrate on recovery and parenting skills. Identification of services for perinatal substance users that are associated with more successful child welfare outcomes has implications for the child welfare system, treatment providers, courts and families.
doi:10.1186/1477-7517-7-19
PMCID: PMC2944302  PMID: 20807432
20.  Parenting Intervention for Externalizing Behavior Problems in Children Born Premature: An Initial Examination 
Objective
To examine the initial efficacy of parent-child interaction therapy (PCIT) for treating behavior problems in young children who were born premature.
Method
In this randomized, controlled trial, 28 children between the ages of 18 and 60 months, who were born <37 weeks gestation and presented with clinically significant externalizing behavior problems, were randomly assigned to an immediate treatment (IT) or waitlist (WL) control group.
Results
After 4 months, children who received PCIT were reported by their mother to have less attention problems, aggressive behaviors, and externalizing and internalizing behavior problems, and they were observed to be more compliant to maternal commands than children in the WL group. In addition, mothers in the IT group interacted more positively with their child, reported lower parenting stress related to difficult child behavior and demonstrated improved parenting practices compared with WL mothers. Behavior change maintained for 80% of the IT children 4 months after treatment completion.
Conclusions
This study demonstrates preliminary efficacy of PCIT for the treatment of behavior problems in young children who were born premature.
doi:10.1097/DBP.0b013e3181d5a294
PMCID: PMC2866142  PMID: 20375736
parent-child interaction therapy; behavior problems; prematurity
21.  Maternal depression and neurobehavior in newborns prenatally exposed to methamphetamine 
Neurotoxicology and teratology  2008;31(3):177-182.
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
22.  The Effect of Parenting Stress on Child Behavior Problems in High-Risk Children with Prenatal Drug Exposure 
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
23.  Novel biomarkers of prenatal methamphetamine exposure in human meconium 
Therapeutic drug monitoring  2009;31(1):70-75.
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
24.  Longitudinal Study of Maternal Report of Sleep Problems in Children with Prenatal Exposure to Cocaine and Other Drugs 
Behavioral sleep medicine  2009;7(4):196-207.
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
25.  Patterns of Methamphetamine Use During Pregnancy: Results from the Infant Development, Environment, and Lifestyle (IDEAL) Study 
Maternal and Child Health Journal  2009;14(4):519-527.
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

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