Little is known about arousal to socially stressful situations in children with Autism Spectrum Disorders. This preliminary study investigates physiologic arousal in children with high functioning autism (HFA, n=19) compared to a comparison group (n=11) before, during, and after the Trier Social Stress Test. The HFA group was more likely to have a decrease in salivary cortisol following the stressor, while the comparison group was more likely to have an increase (p=.02). However, there was no difference in electrodermal activity, a measure of sympathetic arousal, or vagal tone, a measure of parasympathetic activity, between groups. These findings implicate a differential neuroendocrine response to social stress in children with HFA despite similar sympathetic and parasympathetic responses during a stressor. Further studies are required to substantiate this finding.
psychophysiology; Trier Social Stress Test; high functioning autism; stress
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.
autism; infancy; cry; vocalizations; acoustic analysis
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.
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.
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.
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.
infant; motor quality; central nervous system; depression; pregnancy; treatment
We sought to determine if maternal depression, anxiety, and/or treatment with selective serotonin reuptake inhibitors (SSRIs) affect placental human serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) gene expression.
Relative mRNA expression was compared among placental samples (n=164) from healthy women, women with untreated depression and/or anxiety symptoms during pregnancy, and women who used SSRIs.
SLC6A4 expression was significantly increased in placentas from women with untreated mood disorders and from women treated with SSRIs, compared to controls. SLC6A2 and 11β-HSD2 expression was increased in non-control groups, though the differences were not significant. SLC6A4, SLC6A2, and 11β-HSD2 expression levels were positively correlated.
The finding that maternal depression/anxiety affects gene expression of placental SLC6A4 suggests a possible mechanism for the effect(s) of maternal mood on fetal neurodevelopmental programming. SSRI treatment does not further alter the elevated SLC6A4 expression levels observed with exposure to maternal depression or anxiety.
serotonin transporter; norepinephrine transporter; 11beta-hydroxysteroid dehydrogenase; depression; anxiety; placenta; fetal programming
To study white matter integrity using diffusion tensor imaging (DTI) in adolescents with prenatal cocaine and/or tobacco exposure.
Subjects included 20 adolescents with prenatal cocaine exposure (15 with tobacco exposure) and 20 non-cocaine-exposed subjects (8 with tobacco exposure). DTI measures were assessed in 5 subregions of the corpus callosum. The Sensation Seeking Scale for Children was administered to evaluate behavioral inhibition.
No significant differences were found between cocaine-exposed and non-cocaine-exposed group in each subregion of the corpus callosum on measures of fractional anisotropy (FA) and mean diffusivity (MD), although the cocaine-exposed showed a trend (P = 0.06) toward higher FA in projections to the supplementary motor area (SMA) and premotor cortex (PMC) . Prenatal tobacco exposure was associated with decreased FA in SMA-PMC projections after adjustment for relevant covariates (P = 0.03). Decreased FA was related to more sensation seeking in the adolescents who were prenatally exposed to tobacco.
Prenatal tobacco exposure could affect white matter integrity which is related to sensation seeking in adolescents. Developmental neurotoxins might have differential influences on white matter maturation in adolescence.
neuroimaging; impulsivity; prenatal drug exposure; response inhibition
While there is good evidence that depression negatively impacts mother-to-infant emotional attachment in the postpartum period, the impact of depression in pregnancy on maternal emotions and cognitions about the fetus (often termed “maternal–fetal attachment” or MFA) is unclear. This study compared MFA scores from women meeting clinical criteria for Major Depressive Disorder (MDD) with scores from nondepressed women. Participants were 161 women enrolled at 23–36 weeks gestation, of whom 65 met criteria for MDD via the Structured Clinical Interview for the DSM-IV-TR during their second and/or third trimesters. Cranley’s Maternal Fetal Attachment Scale was administered at 26 and 36 weeks gestation. Generalized linear modeling was used to assess the effect of MDD, anxiety, and antidepressant use on MFA. MDD was negatively related to MFA (LR)=4.58, df=1, p<0.04). Neither anxiety (LR=0.22, p<0.64), nor antidepressant use (LR=0.20, df=1, p<0.66) were related to MFA. Depression severity was negatively related to MFAS scores (B=−0.005, SE=.002, p<0.0012) when including the interaction of MDD group and HRSD scores in the model. This study is the first to demonstrate that clinically defined MDD during pregnancy negatively impacts MFA, suggesting that the basis for poor mother-to-infant attachment in postpartum MDD may have roots in pregnancy.
Depression; Pregnancy; Mother–infant relationship
To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.
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.
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).
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.
Prenatal cocaine exposure; small for gestational age; childhood growth
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.
To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure.
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.
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.
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.
Behavior disorder; child behavior; mental health; screening; prenatal cocaine exposure; Pediatric Symptom Checklist
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.
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).
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.
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.
Prenatal cocaine exposure; prenatal alcohol exposure; childhood obesity; growth; fetal origins
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.
Subjects were 412 mother-infant dyads, recruited at birth, participating in a longitudinal study examining the effects of prenatal methamphetamine (MA) 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 mos. 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 IQ. 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, demographic, and socioeconomic covariates.
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 MA exposure was not associated with 3 year-old outcomes, nor did it alter the protective effects of an easier temperament on child behavior.
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.
Prenatal substance exposure; methamphetamine; temperament; child development; child behavior
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.
preterm; neurobehavior; NNNS; NICU; very-low-birthweight infants; single-room NICU design; epigenetics
Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants.
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.
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.
Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress.
Prenatal exposure; Methamphetamine; Neurodevelopment; Meconium
We previously reported an association between prenatal cocaine exposure (PCE) and childhood behavior problems as observed by the parent or caretaker. However, these behavior problems may not manifest in a structured environment, such as a school setting.
We determined whether there is an association between PCE and school behavior problems and whether ratings of behavior problems from the teacher differ from those noted by the parent or caretaker.
The Maternal Lifestyle Study, a multicenter study, enrolled 1388 children with and without PCE at one month of age for longitudinal assessment. Teachers masked to prenatal drug exposure status completed the Teacher Report Form (TRF/6-18) when children were 7, 9, and 11 years old. We also administered the Child Behavior Checklist-parent report (CBCL) to the parent/caretaker at same ages and then at 13 years. We performed latent growth curve modeling to determine whether high PCE will predict externalizing, internalizing, total behavior, and attention problems at 7 years of age and whether changes in problems' scores over time differ between those exposed and non-exposed from both teacher and parent report. Besides levels of PCE as predictors, we controlled for the following covariates, namely: site, child characteristics (gender and other prenatal drug exposures), family level influences (maternal age, depression and psychological symptomatology, continuing drug use, exposure to domestic violence, home environment, and socioeconomic status), and community level factors (neighborhood and community violence).
The mean behavior problem T scores from the teacher report were significantly higher than ratings by the parent or caretaker. Latent growth curve modeling revealed a significant relationship between intercepts of problem T scores from teacher and parent ratings; i.e., children that were rated poorly by teachers were also rated poorly by their parent/caretaker or vice versa. After controlling for covariates, we found high PCE to be a significant predictor of with higher externalizing behavior problem T scores from both parent and teacher report at 7 years (p=0.034 and p=0.021, respectively) in comparison to non-PCE children. These differences in scores from either teacher or caregiver were stable through subsequent years or did not change significantly over time. Boys had higher T scores than girls on internalizing and total problems by caretaker report; they also had significantly higher T scores for internalizing, total, and attention problems by teacher ratings; the difference was marginally significant for externalizing behavior (p=0.070). Caretaker postnatal use of tobacco, depression, and community violence were significant predictors of all behavior problems rated by parent/caretaker, while lower scores on the home environment predicted all behavior outcomes by the teacher report.
Children with high PCE are likely to manifest externalizing behavior problems; their behavior problem scores at 7 years from either report of teacher or parent remained higher than scores of non-exposed children on subsequent years. Screening and identification of behavior problems at earlier ages could make possible initiation of intervention, while considering the likely effects of other confounders.
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.
To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age.
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.
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.
There were no differences in cognition as assessed by the BSID-II between the groups. There was a subtle MA exposure effect on fine motor performance at 1 year with the poorest performance observed in the most heavily exposed children. By 3 years, no differences in fine motor performance were observed. These findings suggest MA exposure has modest motor effects at 1 year that are mostly resolved by 3 years.
prenatal exposure; neurodevelopment; Bayley; Peabody
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.
drug; amphetamine; antenatal; small for gestational age
Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school aged children.
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.
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.
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.
prenatal cocaine exposure; cortisol reactivity; environmental adversity
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.
Methamphetamine; Pregnancy; Alcohol and other drug use; Women; Epidemiology
To determine whether Neonatal Intensive Care Unit Network Neurobehavior Scales (NNNS) at 44 weeks predict motor outcome at 2 years in preterm infants from the Maternal Lifestyles Study (MLS).
Data were collected on all preterm infants (<36 weeks) in the MLS who had an NNNS at 44 weeks (n=395) and neurologic exam at 12–36 months or Bayley Psychomotor Development Index (PDI) at 24 months (n=270). Logistic regression analyzed NNNS summary scores associated with Cerebral Palsy (CP) or PDI <70, while controlling for birth weight 1250g.
Eighteen of 395 infants (5%) had CP; 24 of 270 infants (9%) had PDI <70. CP was associated with low quality of movement (OR 1.95, 95% CI 1.24–3.06, p=0.004) and high lethargy (OR 1.67, 95% CI 1.01–2.76, p=0.045). The model contributed 19% of the variance in CP diagnosis at 12–36 months (R2=0.19, p<0.001). Low PDI was associated with low handling (OR 1.83; 95% CI 1.12–2.99, p=0.017), low quality of movement (OR 2.16; 95%CI 1.38–3.38, p=0.001), and hypotonia (OR 1.63; 95% CI 1.14–2.32, p=0.007). The model contributed 26% of the variance in PDI <70 at 24 months (R2=0.26, p<0.001).
The neurobehavioral profile of underarousal in 44 week preterm infants may predict poor motor outcome.
neurobehavior; outcomes; ELBW
Prenatal cocaine exposure has been linked to intrauterine growth retardation and poor birth outcomes; little is known about the effects on longer-term medical outcomes, such as overweight status and hypertension in childhood. Our objective was to examine the association between prenatal cocaine exposure and body mass index and blood pressure at 9 years of age among children followed prospectively in a multi-site longitudinal study evaluating the impact of maternal lifestyle during pregnancy on childhood outcome.
This analysis includes 880 children (277 cocaine exposed and 603 with no cocaine exposure) with blood pressure, height, and weight measurements at 9 years of age. Regression analyses were conducted to explore the relationship between prenatal cocaine exposure and body mass index and blood pressure at 9 years of age after controlling for demographics, other drug exposure, birth weight, maternal weight, infant postnatal weight gain, and childhood television viewing, exercise and dietary habits at 9 years. Path analyses were used to further explore these relationships.
At 9 years of age, 15% of the children were pre-hypertensive and 19% were hypertensive; 16% were at risk for overweight status and 21% were overweight. A small percentage of women were exposed to high levels of prenatal cocaine throughout pregnancy. Among children born to these women, a higher body mass index was noted. Path analysis suggested that high cocaine exposure has an indirect effect on systolic and diastolic blood pressure that is mediated through its effect on body mass index.
High levels of in-utero cocaine exposure are a marker for elevated body mass index and blood pressure among children born full term.
Prenatal cocaine exposure; Body mass index; Childhood hypertension; Overweight; Obesity
We evaluated prenatal substance use in a cohort of 480 HIV-infected women and their uninfected children. Substance use was reported by 29%; the most common substances reported were tobacco (18%), alcohol (10%), and marijuana (7.2%). Fewer than 4% of women reported cocaine or opiate use. Substance use was more common in the first trimester (25%) than the second (17%) and third (15%) (trend p-value < 0.01), and was associated with race/ethnicity, education, birthplace, age and marital status. For 264 mother/infant pairs with meconium results, sensitivity of self-report was 86% for tobacco, 80% for marijuana and 67% for cocaine. Higher discordance between self-report and urine/blood toxicology was observed for cocaine, marijuana and opiates in a non-random subset of mothers/infants with these tests. Findings suggest reasonably complete self-reporting of substance use as confirmed by meconium analysis. Illicit substance use was low and substantially less than that reported in earlier studies of HIV-infected women, but alcohol and tobacco exposure was prevalent.
substance use; prenatal exposure; meconium; HIV
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.
Immunoassay-positive and -negative meconium samples were subjected to liquid chromatography–tandem mass spectrometric reanalysis for these recently identified metabolites.
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.
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.
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.
Sleep data was collected by maternal report in a prospective longitudinal follow-up of children participating in the Maternal Lifestyle multisite study.
Hospital based research centers in Providence, RI, Miami, FL, Detroit, MI, and Memphis, TN
There were 808 participants: 374 exposed to cocaine and/or opiates; 434 comparison.
Prenatal cocaine, opiate, marijuana, alcohol, and nicotine exposure.
Sleep problems in early, middle, and late childhood, assessed as composites of maternal report items.
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.
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.
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.
Childhood obesity; premature birth; infant SGA; birth weight; exercise; prenatal drug exposure