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1.
Neurotoxicol Teratol ; 51: 35-44, 2015.
Article in English | MEDLINE | ID: mdl-26212684

ABSTRACT

This study reviews the findings from the Infant Development, Environment, and Lifestyle (IDEAL) study, a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children. No neonatal abstinence syndrome requiring pharmacologic intervention was observed but heavy drug exposure was associated with increased stress responses in the neonatal period. Poorer inhibitory control was also observed in heavy methamphetamine exposed children placing them at high risk for impaired executive function. Independent of methamphetamine exposure, children with more responsive home environments to developmental and emotional needs demonstrated lower risks for internalizing and externalizing behavior.


Subject(s)
Central Nervous System Stimulants/adverse effects , Developmental Disabilities/chemically induced , Life Style , Methamphetamine/adverse effects , Prenatal Exposure Delayed Effects , Animals , Female , Humans , Infant , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/physiopathology , Prenatal Exposure Delayed Effects/psychology
2.
Subst Abus ; 35(1): 68-73, 2014.
Article in English | MEDLINE | ID: mdl-24588296

ABSTRACT

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.


Subject(s)
Child Development/drug effects , Methamphetamine/adverse effects , Prenatal Exposure Delayed Effects/psychology , Case-Control Studies , Female , Humans , Infant, Newborn , Longitudinal Studies , Male , Neuropsychological Tests , Pregnancy
3.
J Stud Alcohol Drugs ; 74(3): 447-51, 2013 May.
Article in English | MEDLINE | ID: mdl-23490574

ABSTRACT

OBJECTIVE: Until now, the functioning of the hypothalamic-pituitary-adrenal (HPA) axis in children with prenatal methamphetamine exposure (PME) had been unexamined. Previous research indicates that prenatal exposure to stimulant drugs is associated with dose-response alterations in neural growth and connectivity and consequent neurobehavioral deficits. In addition, children of drug-using parents are at an increased risk for exposure to chronic postnatal stress. In this preliminary study, we examined the associations of PME and postnatal environmental stress with cortisol stress reactivity in children with PME. METHOD: Participants were 2-year-old children (N = 123; 55.3% male) with PME from a multicenter longitudinal Infant, Development, Environment, and Lifestyle Study. Saliva samples were obtained before and after a stress-inducing separation task. Hierarchical multiple regression analyses examined prenatal drug exposure, methodological and postnatal stress covariates, and interactions between levels of PME and postnatal stress. RESULTS: Mild to moderate potential for child physical abuse moderated increased cortisol reactivity in high exposed children with PME. Blunted cortisol reactivity was associated with caregiver's postnatal alcohol use, child's behavioral dysregulation, and the interaction between higher levels of PME and caregiver's psychopathology. CONCLUSIONS: Consistent with the known effects of stimulant drugs and chronically stressful environments on the HPA axis and, thus, the toxic stress and allostatic load phenomena, our results imply that elevated PME may be associated with alterations in the programming of the HPA axis reflecting hyperactivity, which under significant and chronic environmental stress then may become hypoactive.


Subject(s)
Hydrocortisone/metabolism , Methamphetamine/adverse effects , Prenatal Exposure Delayed Effects/metabolism , Stress, Physiological , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Amphetamine-Related Disorders/complications , Caregivers , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/adverse effects , Child, Preschool , Female , Follow-Up Studies , Humans , Hypothalamo-Hypophyseal System/metabolism , Longitudinal Studies , Male , Methamphetamine/administration & dosage , Pituitary-Adrenal System/metabolism , Pregnancy , Prospective Studies , Saliva/metabolism , Stress, Psychological/metabolism
4.
Child Psychiatry Hum Dev ; 43(6): 943-57, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22552952

ABSTRACT

The present study was designed to examine parenting stress, maternal depressive symptoms, and perceived child behavior problems among mothers who used methamphetamine (MA) during pregnancy. Participants were a subsample (n = 212; 75 exposed, 137 comparison) of biological mothers who had continuous custody of their child from birth to 36 months. The subsample was drawn from a larger, ongoing longitudinal study on the effects of prenatal methamphetamine exposure (n = 412; 204 exposed, 208 comparison) (Arria et al in Matern Child Health J 10:293-302 2006). Mothers who used MA during pregnancy reported more parenting stress and more depressive symptoms than a matched comparison group. There were no differences between groups on perceived child behavior problems. In a hierarchical linear model, depressive symptoms, and perceived child behavior problems, but not MA exposure, were statistically significant predictors of parenting stress. Screening for potential parenting problems among mothers with a history of substance abuse is warranted. Parenting interventions targeting depressive symptoms, parenting stress, and child behavior problems are needed for this population.


Subject(s)
Central Nervous System Stimulants/adverse effects , Child Behavior Disorders/epidemiology , Depression/epidemiology , Methamphetamine/adverse effects , Mothers/psychology , Stress, Psychological/epidemiology , Adult , Child Behavior Disorders/psychology , Child, Preschool , Cohort Studies , Depression/psychology , Female , Hawaii/epidemiology , Humans , Mother-Child Relations , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/psychology , Stress, Psychological/psychology , Young Adult
5.
Depress Anxiety ; 29(6): 515-22, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22555777

ABSTRACT

BACKGROUND: Maternal depression is associated with a higher incidence of behavioral problems in infants, but the effects of maternal depression as early as 1 month are not well characterized. The objective of this study is to determine the neurobehavioral effects of maternal depression on infants exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS). METHODS: Four hundred twelve mother-infant pairs were enrolled (MA = 204) and only biological mothers with custody of their child were included in the current analysis. At the 1-month visit (n = 126 MA-exposed; n = 193 MA-unexposed), the Beck Depression Inventory-II (BDI-II) was administered, and the NNNS was administered to the infant. Exposure was identified by self-report and/or gas chromatography/mass spectroscopy confirmation of amphetamine and metabolites in newborn meconium. Unexposed subjects were matched, denied amphetamine use, and had negative meconium screens. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS, with significance accepted at P < .05. RESULTS: The MA group had an increased incidence of depression-positive diagnosis and increased depression scores on the BDI-II. After adjusting for covariates, MA exposure was associated with increased arousal and handling scores, and a decreased ability to self-regulate. Maternal depression was associated with higher autonomic stress and poorer quality of movement. No additional differences were observed in infants whose mothers were both depressed and used MA during pregnancy. CONCLUSIONS: Maternal depression is associated with neurodevelopmental patterns of increased stress and decreased quality of movement, suggesting maternal depression influences neurodevelopment in infants as young as 1 month.


Subject(s)
Child Development , Depressive Disorder/complications , Infant, Newborn, Diseases/etiology , Methamphetamine/toxicity , Mothers/psychology , Prenatal Exposure Delayed Effects , Adult , Arousal/drug effects , Central Nervous System Stimulants/toxicity , Depressive Disorder/psychology , Developmental Disabilities/etiology , Developmental Disabilities/psychology , Female , Humans , Infant Behavior/drug effects , Infant Behavior/psychology , Infant, Newborn , Infant, Newborn, Diseases/psychology , Life Style , Longitudinal Studies , Male , Motor Activity/drug effects , Pregnancy , Social Environment , Socioeconomic Factors , Stress, Psychological/etiology , Stress, Psychological/psychology , Substance-Related Disorders/complications , Young Adult
6.
Am J Perinatol ; 29(5): 391-400, 2012 May.
Article in English | MEDLINE | ID: mdl-22399214

ABSTRACT

OBJECTIVE: Examine maternal and infant medical outcomes of prenatal exposure to methamphetamine (MA). STUDY DESIGN: Four hundred and twelve mother-infant pairs (204 MA-exposed and 208 unexposed matched comparisons) were enrolled in the Infant Development, Environment and Lifestyle (IDEAL) study. Exposure was determined by maternal self-report during this pregnancy and/or positive meconium toxicology. Maternal interviews assessed prenatal drug use, pregnancy course, and sociodemographic information. Medical chart reviews provided medical history, obstetric complications, infant outcomes, and discharge placement. RESULTS: MA-using mothers were more likely to be poor, to have a psychiatric disorder/emotional illness and less prenatal care, and to be less likely to breast-feed their infant than comparison mothers. After adjusting for covariates, MA-exposed infants were more likely to exhibit poor suck, to have smaller head circumferences and length, to require neonatal intensive care unit (NICU) admission, and to be referred to child protective services (CPS). Several outcomes previously reported from studies that lacked adequate control groups or adjustment for covariates were not significantly different in this study. CONCLUSION: Prenatal MA exposure is associated with maternal psychiatric disorder/emotional illness, poor suck, NICU admission, and CPS involvement, and MA-exposed infants were less likely to be breast-fed; however, the absence of many serious complications, such as fetal distress, chronic hypertension, preeclampsia, placenta previa, abruptio placentae, and cardiac defects, suggests confounding variables influenced prior studies.


Subject(s)
Central Nervous System Stimulants/adverse effects , Maternal Exposure/adverse effects , Methamphetamine/adverse effects , Adult , Body Height , Breast Feeding/statistics & numerical data , Cephalometry , Child , Child Welfare/statistics & numerical data , Female , Humans , Infant, Newborn , Intensive Care Units, Neonatal/statistics & numerical data , Matched-Pair Analysis , Mental Disorders/epidemiology , Patient Admission/statistics & numerical data , Poverty , Pregnancy , Prenatal Care/statistics & numerical data , Sucking Behavior
7.
Am J Perinatol ; 29(3): 203-10, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21818727

ABSTRACT

We examined the effects of prenatal methamphetamine (MA) exposure on growth parameters from birth to age 3 years. The 412 subjects included (n = 204 exposed) were enrolled at birth in the Infant Development, Environment and Lifestyle study, a longitudinal study assessing the effects of prenatal MA exposure on childhood outcomes. Individual models were used to examine the effects of prenatal MA exposure on weight, head circumference, height, and weight-for-length growth trajectories. After adjusting for covariates, height trajectory was lower in the exposed versus the comparison children (p = 0.021) over the first 3 years of life. Both groups increased height on average by 2.27 cm per month by age 3 years. In term subjects, MA exposure was also associated with a lower height trajectory (p = 0.034), with both the exposed and comparison groups gaining 2.25 cm per month by age 3 years. There was no difference in weight, head circumference, or weight-for-length growth trajectories between the comparison and the exposed groups. Children exposed prenatally to MA have a modest decrease in height growth trajectory during the first 3 years of life with no observed difference in weight, head circumference, or weight-for-length trajectories.


Subject(s)
Central Nervous System Stimulants/adverse effects , Child Development/drug effects , Methamphetamine/adverse effects , Prenatal Exposure Delayed Effects , Adult , Birth Weight/drug effects , Body Size/drug effects , Case-Control Studies , Child, Preschool , Female , Humans , Infant , Longitudinal Studies , Male , Pregnancy
8.
Am J Med Genet A ; 155A(4): 748-56, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21594997

ABSTRACT

We describe an infant male of Cambodian background who has typical craniofacial features of mycophenolate mofetil (MMF) embryopathy and a complex congenital heart defect (CHD) (double outlet right ventricle, mitral atresia, pulmonic stenosis, and total anomalous pulmonary venous return). Together with four case reports and the 20 patients included in two recent reviews, we report 24 (19 affected, five normal) patients with this pattern of anomalies. Eight (33%) have a CHD, most commonly, conotruncal or aortic arch defects (6/8, 75%). This would support the hypothesis that disturbance of cranial neural crest migration occurs in exposed infants, and may predict which additional anomalies will be observed in the future. We also attempted to score the severity of the facial anomalies in each MMF patient using a system created by plastic surgeons for patients with hemifacial microsomia. This classification had modest utility in comparing severity and correlating facial to extracranial defects. The findings are viewed with caution because of the preliminary methodology. Finally, since several exposed infants have been reported to be minimally affected, we remind clinicians to be sensitive to the potential mild expression of the effects of this teratogen. This awareness may influence clinical management of apparently normal MMF-exposed individuals.


Subject(s)
Face/abnormalities , Fetal Diseases/chemically induced , Fetal Diseases/diagnosis , Heart Defects, Congenital/chemically induced , Immunosuppressive Agents/adverse effects , Mycophenolic Acid/analogs & derivatives , Phenotype , Female , Humans , Infant, Newborn , Male , Middle Aged , Mycophenolic Acid/adverse effects , Pregnancy
9.
Neurotoxicol Teratol ; 33(1): 176-84, 2011.
Article in English | MEDLINE | ID: mdl-21256431

ABSTRACT

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.


Subject(s)
Child Behavior/psychology , Child Development/drug effects , Cognition/drug effects , Methamphetamine/toxicity , Motor Activity/drug effects , Prenatal Exposure Delayed Effects/chemically induced , Case-Control Studies , Child Behavior/drug effects , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant Behavior/drug effects , Infant Behavior/psychology , Infant, Newborn , Longitudinal Studies , Male , Pregnancy , Prenatal Exposure Delayed Effects/physiopathology , Prenatal Exposure Delayed Effects/psychology , Social Class , Surveys and Questionnaires
10.
J Dev Behav Pediatr ; 32(2): 125-35, 2011.
Article in English | MEDLINE | ID: mdl-21200329

ABSTRACT

OBJECTIVE: This study examined the role that easy infant temperament and cumulative environmental risk play in predicting cognitive, language, and behavioral outcomes in 3-year-old children at high social risk. METHODS: Subjects were 412 mother-infant dyads, recruited at birth, participating in a longitudinal study examining the effects of prenatal methamphetamine on child development. This analysis includes a subsample (n = 290) of the study with a completed 3-year visit. Temperament was assessed by the Infant Behavior Questionnaire at 12 months. Factor analysis from well-validated measures generated "easy" and "difficult" temperament profiles and a profile for high-risk environment. Caretaker receptive vocabulary served as a proxy for intelligence quotient. Outcomes at 3 years included motor and mental development, behavior problems, and language. Linear regression and hierarchical linear modeling examined the effects of temperament, high-risk environment, and caregiver receptive language on outcomes adjusting for maternal drug use and demographic and socioeconomic covariates. RESULTS: Internalizing and externalizing behaviors were lower in children with easy temperament and higher with increased environmental risk. Easy temperament attenuated behavioral problems only in the setting of lower environmental risk. Caregiver receptive language was associated with lower internalizing scores. High-risk environment and temperament factors were not related to cognitive or motor outcomes. Prenatal methamphetamine exposure was not associated with 3-year-old outcomes, nor did it alter the protective effects of an easier temperament on child behavior. CONCLUSIONS: CHILDREN growing up in adverse social environments had increased behavioral problems and compromised language development. Conversely, an easy temperament acts as a protective factor for social-emotional development and could be related to resilience.


Subject(s)
Child Behavior Disorders/epidemiology , Language Development Disorders/epidemiology , Methamphetamine/adverse effects , Prenatal Exposure Delayed Effects/epidemiology , Social Environment , Temperament , Case-Control Studies , Child, Preschool , Factor Analysis, Statistical , Female , Humans , Linear Models , Longitudinal Studies , Male , Matched-Pair Analysis , Multivariate Analysis , Pregnancy , United States/epidemiology
11.
J Pediatr ; 157(2): 337-9, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20570284

ABSTRACT

Previous studies suggest that prenatal methamphetamine exposure inhibits fetal growth. We examined neonatal growth effects of prenatal methamphetamine exposure in a prospective cohort study. After adjusting for covariates, exposed neonates had a higher incidence of being small for gestational age than unexposed neonates.


Subject(s)
Central Nervous System Stimulants/adverse effects , Fetal Growth Retardation/chemically induced , Maternal Exposure , Methamphetamine/adverse effects , Substance-Related Disorders/complications , Birth Weight , Female , Gestational Age , Humans , Infant, Newborn , Infant, Small for Gestational Age , Male , Pregnancy , Pregnancy Complications , Pregnancy Outcome , Social Class
12.
Clin Chem ; 56(5): 856-60, 2010 May.
Article in English | MEDLINE | ID: mdl-20185623

ABSTRACT

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. Maximizing 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.


Subject(s)
Central Nervous System Stimulants/analysis , Central Nervous System Stimulants/metabolism , Meconium/chemistry , Methamphetamine/analysis , Methamphetamine/metabolism , Substance Abuse Detection/methods , Female , Humans , Infant, Newborn , Pregnancy
13.
Ther Drug Monit ; 31(6): 769-75, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19935364

ABSTRACT

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.


Subject(s)
Amphetamines , Maternal Exposure , Meconium/chemistry , Neurotoxins , Self Disclosure , Substance Abuse Detection/methods , Adolescent , Adult , Amphetamines/analysis , Cannabinoids/analysis , Cotinine/analysis , Female , Humans , Infant, Newborn , Interviews as Topic , Male , Marijuana Smoking , Neurotoxins/analysis , Pregnancy , Pregnancy Trimesters , Sensitivity and Specificity , Smoking , Young Adult
14.
Pediatrics ; 123(6): 1541-7, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19482766

ABSTRACT

OBJECTIVE: We tested the hypothesis that soluble vascular endothelial growth factor receptors are involved in the development of bronchopulmonary dysplasia/chronic lung disease. PATIENTS AND METHODS: Neonates with a birth weight of < or =1500 g and/or < or =30 weeks' gestation, with respiratory failure, requiring O(2) and mechanical ventilation within 24 hours, were eligible. Tracheal aspirate fluid samples were collected from 65 neonates before surfactant and/or assisted mechanical ventilation (baseline), at 3 and 7 days after birth, and weekly thereafter until extubation. Samples were analyzed for total vascular endothelial growth factor, soluble vascular endothelial growth factor receptor 1 and 2 levels and compared in infants with bronchopulmonary dysplasia/chronic lung disease (n = 31) versus those with no bronchopulmonary dysplasia/chronic lung disease (n = 34). RESULTS: Mean gestational age and birth weight were lower in infants with bronchopulmonary dysplasia/chronic lung disease. At baseline, vascular endothelial growth factor levels in the tracheal aspirate fluid were significantly lower, whereas soluble vascular endothelial growth factor receptor 1 levels were higher in the bronchopulmonary dysplasia/chronic lung disease infants compared with infants with no bronchopulmonary dysplasia/chronic lung disease. Vascular endothelial growth factor levels progressively increased from baseline to 4 weeks in all of the infants developing bronchopulmonary dysplasia/chronic lung disease. Conversely, soluble vascular endothelial growth factor receptor 1 declined in both groups from baseline to 5 weeks of age. Similarly, soluble vascular endothelial growth factor receptor 2 declined from baseline to 5 weeks in the control infants, but there were significant increases at 3 and 4 weeks in infants developing bronchopulmonary dysplasia/chronic lung disease. CONCLUSIONS: We speculate that low vascular endothelial growth factor levels in tracheal aspirate fluid, concurrent with elevated soluble vascular endothelial growth factor receptor 1 levels on the first day of life, are biological markers for the development of bronchopulmonary dysplasia/chronic lung disease in very low birth weight infants requiring O(2) and assisted mechanical ventilation.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Bronchopulmonary Dysplasia/diagnosis , Infant, Very Low Birth Weight , Respiration, Artificial , Respiratory Distress Syndrome, Newborn/therapy , Vascular Endothelial Growth Factor Receptor-1/analysis , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Intensive Care Units, Neonatal , Male , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Factors , Suction , Trachea/chemistry , Vascular Endothelial Growth Factor Receptor-2/analysis , Ventilator Weaning
15.
Ther Drug Monit ; 31(1): 70-5, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19125148

ABSTRACT

Meconium analysis can detect fetal exposure to drugs taken by the mother during pregnancy. Methamphetamine (MAMP) and amphetamine (AMP) have previously been observed in meconium of MAMP-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. Forty-three MAMP-positive meconium specimens were analyzed for newly identified MAMP biomarkers, p-hydroxymethamphetamine, p-hydroxyamphetamine, and norephedrine. Due to MAMP adulteration in illicit ecstasy and to simultaneously monitor 3,4-methylenedioxymethamphetamine and MAMP prenatal exposure, 3,4-methylenedioxymethamphetamine, its metabolites, and related sympathomimetic amines were assayed. MAMP, AMP, and unconjugated p-hydroxymethamphetamine were the most prevalent and abundant analytes present in meconium; however, unconjugated p-hydroxyamphetamine and norephedrine also were identified. 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 MAMP at specific gestational ages or with different metabolic capabilities. Although these new biomarkers were present in lower concentrations than MAMP and AMP in the meconium of previously confirmed specimens, additional research will determine if inclusion of these analytes can increase identification of MAMP-exposed neonates. Novel methamphetamine biomarker concentrations were characterized in meconium of infants exposed in utero to MAMP.


Subject(s)
Central Nervous System Stimulants/pharmacokinetics , Meconium/chemistry , Methamphetamine/pharmacokinetics , Adult , Biomarkers , Biotransformation , Chromatography, High Pressure Liquid , Female , Gestational Age , Humans , Infant, Newborn , Mass Spectrometry , Pregnancy , Pregnancy Outcome , Sympathomimetics/analysis , Young Adult
16.
Neurotoxicol Teratol ; 31(3): 177-82, 2009.
Article in English | MEDLINE | ID: mdl-19059478

ABSTRACT

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.


Subject(s)
Depression/chemically induced , Infant, Newborn, Diseases/psychology , Lethargy/chemically induced , Methamphetamine/pharmacology , Prenatal Exposure Delayed Effects , Puerperal Disorders/chemically induced , Arousal/drug effects , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/chemically induced , Pregnancy , Puerperal Disorders/psychology
17.
Neurotoxicol Teratol ; 30(1): 20-8, 2008.
Article in English | MEDLINE | ID: mdl-18031987

ABSTRACT

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.


Subject(s)
Central Nervous System Stimulants/adverse effects , Methamphetamine/adverse effects , Neonatal Abstinence Syndrome/etiology , Prenatal Exposure Delayed Effects , Female , Humans , Infant, Newborn , Male , Neonatal Abstinence Syndrome/epidemiology , Neonatal Abstinence Syndrome/physiopathology , Pregnancy , Pregnancy Outcome , Retrospective Studies
18.
Sleep Breath ; 12(2): 169-78, 2008 May.
Article in English | MEDLINE | ID: mdl-17924156

ABSTRACT

Oral appliances (OAs) have been used to treat obstructive sleep apnea (OSA) patients for decades. However, detailed dental side effects in long-term OA cases analyzed with an accurate three-dimensional (3D) measurement tool have seldom been reported. The purpose of this study is to evaluate dental side effects in five OSA patients, who had used a tongue retaining device (TRD) (with occasional other OA wear) for an average of 6 years and 4 months. The baseline and follow-up orthodontic study models were measured with a newly developed MicroScribe-3DX analysis system. High compliance of TRD wear was confirmed in all cases and different patterns and amounts of dental changes were observed. The most common appliance-induced dental changes included anterior and/or unilateral posterior open-bites and reduced anterior overjets. It was hypothesized that there might be two possible mechanisms for the TRD side effects--one is the forward pressure of the tongue upon the anterior dental arch and the other is the lateral pressure of the tongue upon the posterior arch. Considerations to correct the TRD dental side effects should be guided by these different mechanisms of the tongue on the dental arch. Possible solutions to minimize occlusal changes and maximize the benefits for OSA patients are also discussed.


Subject(s)
Dental Arch/diagnostic imaging , Imaging, Three-Dimensional , Orthodontic Appliances, Removable/adverse effects , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Snoring/etiology , Snoring/prevention & control , Tomography, X-Ray Computed , Tongue , Adult , Female , Follow-Up Studies , Humans , Male , Mandibular Advancement , Middle Aged , Polysomnography , Tongue Habits
19.
Am J Drug Alcohol Abuse ; 33(2): 281-9, 2007.
Article in English | MEDLINE | ID: mdl-17497551

ABSTRACT

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.


Subject(s)
Amphetamine-Related Disorders/psychology , Maternal Behavior , Methamphetamine , Parenting , Pregnancy Complications/psychology , Analysis of Variance , Child Development , Female , Humans , Infant , Infant Welfare , Longitudinal Studies , Mental Health , Poverty Areas , Pregnancy , Risk Factors , United States
20.
Pediatrics ; 118(3): 1149-56, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16951010

ABSTRACT

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.


Subject(s)
Central Nervous System Stimulants/adverse effects , Fetal Growth Retardation/chemically induced , Methamphetamine/adverse effects , Poverty , Substance-Related Disorders/complications , Adult , Birth Weight , Female , Fetal Growth Retardation/economics , Humans , Infant, Newborn , Infant, Small for Gestational Age , Male , Pregnancy , Pregnancy Outcome , Prospective Studies , Risk Factors
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