Gestational weight gain, prepregnancy body mass index and offspring attention-deficit hyperactivity disorder symptoms and behaviour at age 10.

OBJECTIVE: To assess offspring attention-deficit hyperactivity disorder (ADHD) symptoms and emotional/behavioural impairments at age 10 years in relation to maternal gestational weight gain (GWG) and prepregnancy body mass index (BMI). DESIGN AND SETTING: Longitudinal birth cohort from Magee-Womens Hospital, Pittsburgh, Pennsylvania (enrolled 1983-86). POPULATION: Mother-infant dyads (n = 511) were followed through pregnancy to 10 years. METHODS: Self-reported total GWG was converted to gestational-age-standardised z-scores. Multivariable linear and negative binomial regressions were used to estimate effects of GWG and BMI on outcomes. MAIN OUTCOME MEASURES: Child ADHD symptoms were assessed with the Conners' Continuous Performance Test. Child behaviour was assessed by parent and teacher ratings on the Child Behaviour Checklist (CBCL) and Teacher Report Form, respectively. RESULTS: The mean (SD) total GWG (kg) was 14.5 (5.9), and 10% of women had a pregravid BMI ≥30 kg/m2 . Prepregnancy obesity (BMI of 30 kg/m2 ) was associated with increased offspring problem behaviours including internalising behaviours (adjusted ß 3.3 points, 95% CI 1.7-4.9), externalising behaviours (adjusted ß 2.9 points, 95% CI 1.4-4.6), and attention problems (adjusted ß 2.3 points, 95% CI 1.1-3.4) on the CBCL, compared with normal weight mothers (BMI of 22 kg/m2 ). There were nonsignificant trends towards increased offspring impulsivity with low GWG among lean mothers (adjusted incidence rate ratio 1.2, 95% CI 0.9-1.5) and high GWG among overweight mothers (adjusted incidence rate ratio 1.7, 95% CI 0.9-2.8), but additional outcomes did not differ by GWG z-score. Results were not meaningfully different after excluding high-substance users. CONCLUSIONS: In a low-income and high-risk sample, we observed a small increase in child behaviour problems among children of obese mothers, which could have an impact on child behaviour in the population. TWEETABLE ABSTRACT: Maternal obesity is associated with a small increase in child behaviour problems.

Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults.

BACKGROUND: Studies have demonstrated that an early age of onset of marijuana use (EAOM) is associated with a higher risk of developing psychotic symptoms (PS) compared to initiating marijuana use at a later age or not at all. Research has also found that prenatal marijuana exposure (PME) predicts EAOM. This report evaluates the relationships among PME, EAOM, and PS. METHOD: Subjects were initially interviewed in their fourth prenatal month. Women and offspring who completed the birth assessment (n = 763) were selected for follow-up. Women and their offspring were followed until the offspring were 22 years of age: 596 offspring were evaluated. At age 22, PS were assessed in the offspring with the Diagnostic Interview Schedule using DSM-IV criteria. Analyses controlled for significant covariates including other prenatal substance exposures, race, gender, and offspring substance use at 22 years. RESULTS: PME and EAOM significantly predicted increased rates of PS at 22 years controlling for other significant covariates. The direct effect of PME on PS was marginally significant (p = 0.06) when EAOM was entered into the model and other covariates were fixed. In the mediation analysis, EAOM did not significantly mediate the association between PME and PS, controlling for significant covariates, nor was the indirect pathway significant when structural equation modeling was used. The total effect of the direct and indirect pathways was significant. CONCLUSIONS: In addition to EAOM, PME may also play a role in the association between marijuana use and the development of PS. This could highlight a new area for prevention.

A portable signal causing faithful DNA methylation de novo in Neurospora crassa.

Methylation of cytosine residues in eukaryotic DNA is common, but poorly understood. Typically several percent of the cytosines are methylated; however, it is unclear what governs which sequences eventually become modified. Neurospora crassa DNA containing the "zeta-eta" (zeta-eta) region, which is a region of unusually heavy methylation, was tested for its ability to direct DNA methylation de novo. DNA stripped of its methylation by propagation in Escherichia coli was reintroduced into Neurospora crassa by transformation. The zeta-eta region reproducibly became "properly" methylated whether inserted at its native chromosomal position or at ectopic sites. Adjacent Neurospora and bacterial sequences in the transforming DNA rarely became methylated. A model is presented that accounts for position-independent faithful methylation as observed in the zeta-eta region, as well as position-dependent methylation, as occasionally observed, especially with sequences not native to Neurospora.

Genome-wide copy-number variation study of psychosis in Alzheimer's disease.

About 40-60% of patients with late-onset Alzheimer's disease (AD) develop psychosis, which represents a distinct phenotype of more severe cognitive and functional deficits. The estimated heritability of AD+P is ~61%, which makes it a good target for genetic mapping. We performed a genome-wide copy-number variation (CNV) study on 496 AD cases with psychosis (AD+P), 639 AD subjects with intermediate psychosis (AD intermediate P) and 156 AD subjects without psychosis (AD-P) who were recruited at the University of Pittsburgh Alzheimer's Disease Research Center using over 1 million single-nucleotide polymorphisms (SNPs) and CNV markers. CNV load analysis found no significant difference in total and average CNV length and CNV number in the AD+P or AD intermediate P groups compared with the AD-P group. Our analysis revealed a marginally significant lower number of duplication events in AD+P cases compared with AD-P controls (P=0.059) using multivariable regression model. The most interesting finding was the presence of a genome-wide significant duplication in the APC2 gene on chromosome 19, which was protective against developing AD+P (odds ratio=0.42; P=7.2E-10). We also observed suggestive associations of duplications with AD+P in the SET (P=1.95E-06), JAG2 (P=5.01E-07) and ZFPM1 (P=2.13E-07) genes and marginal association of a deletion in CNTLN (P=8.87E-04). We have identified potential novel loci for psychosis in Alzheimer's disease that warrant follow-up in large-scale independent studies.

Effects of prenatal cocaine/crack and other drug exposure on electroencephalographic sleep studies at birth and one year.

OBJECTIVE: Little is known about the neurophysiologic effects of prenatal cocaine/crack use. The aim of this study, designed to overcome methodologic limitations of previous research, was to investigate the effects of prenatal cocaine use on electroencephalographic (EEG) sleep patterns, a marker of central nervous system development. METHODS: In a longitudinal study of prenatal cocaine/crack exposure, women were interviewed at the end of each trimester about cocaine, crack, alcohol, tobacco, marijuana, and other drug use. Two-hour paper- and computer-generated EEG sleep recordings were obtained on a sample of the full-term infants on the second day of life and at 1 year postpartum. Eligible newborns were full-term, had received no general anesthesia, and had a 5-minute Apgar score >5. All infants whose mothers used one or more lines of cocaine during their first trimester or any crack (n = 37) were selected. A comparison group was chosen randomly from the group of women who did not use cocaine or crack during their pregnancy (n = 34). RESULTS: Women who used cocaine/crack during the first trimester were older, less educated, less likely to be working, and used more tobacco, alcohol, marijuana, and other illicit drugs than women who did not use cocaine/crack during the first trimester. There were no differences in infant birth weight, length, head circumference, or gestational age between the two exposure groups. After controlling for the significant covariates, prenatal cocaine exposure was associated with less well developed spectral correlations between homologous brain regions at birth, and with lower spectral EEG power values at 1 year of age. Prenatal alcohol, marijuana, and tobacco use were found to affect state regulation and cortical activities. CONCLUSIONS: These results indicate that the neurotoxic effects of prenatal cocaine/crack use can be detected with quantitative EEG measures.

Sleep architecture and continuity measures of neonates with chronic lung disease.

Electroencephalographic (EEG) sleep studies of 25 preterm neonates with chronic lung disease (CLD) corrected to a fullterm postconceptional age were compared with recordings from two groups of neonates without CLD: a fullterm appropriate for gestational age group (9 patients) and a preterm group studied at a corrected term postconceptional age (15 patients). Electrographic/polygraphic studies were obtained using 21-channel EEG recordings. Scores were tabulated based on minute-by-minute visual analyses of sleep state, number and duration of arousals, body movements and rapid eye movements (REM). A significant reduction in the percentage of active sleep was noted in the CLD group compared to both control groups (31.15% vs. 47.01% and 52.9%, respectively). The mean percentage of indeterminate sleep was significantly increased in the study group as compared to both control groups (31.23% vs. 15.18% and 11.5%). In addition, significant differences were noted between the CLD group and the healthy preterm control group with respect to the number (0.29/minute vs. 0.13/minute) and duration (4.8 seconds vs. 2.94 seconds) of arousals as well as the total number of body movements (1.57/minute vs. 0.74/minute). These data suggest that neurophysiological organization of the immature brain, as reflected in neonatal sleep architecture and continuity measures, is adversely affected in neonates with CLD. EEG sleep architecture and continuity measures may be helpful in predicting the longitudinal outcome of infants with CLD as this group is at risk for adverse neurodevelopmental outcome.

Prenatal cocaine exposure. A longitudinal study of development.

The current study examines the effect of prenatal cocaine use on physical, cognitive, and behavioral development at birth, 1, 3, and 7 years, controlling for other factors that affect child development. Women who used cocaine during pregnancy were more likely to be single and to use alcohol, marijuana, and tobacco than were women who did not use cocaine. Prenatal cocaine use was associated with reduced gestational age, but not with birth weight, length, or head circumference. Neonatal neurobehavioral assessments were affected by prenatal cocaine exposure. Growth at 1 year was not affected by prenatal cocaine use. At 3 years, prenatal cocaine use was a significant predictor of head circumference and of the composite score on the Stanford-Binet Intelligence Scale (4th edition). Prenatal cocaine use was also associated with temperamental differences at 1 and 3 years and with behavior problems at 3 years. These findings represent a pattern of central nervous system effects, related to prenatal cocaine exposure, which is predicted by the teratologic model.

Detrimental effects of prenatal cocaine exposure: illusion or reality?

OBJECTIVE: The primary purpose of this study is to investigate the impact of prenatal cocaine exposure, while controlling for other factors that influence infant outcome. METHOD: These preliminary data are from an ongoing prospective study of prenatal cocaine and/or crack exposure. Detailed information is collected about the use of cocaine, crack, alcohol, tobacco, marijuana, and other drugs during each trimester of pregnancy. RESULTS: Women who use cocaine and/or crack during pregnancy differ from those who do not. The women who use cocaine are older, more likely to be black, and less likely to be married. They also use more tobacco, alcohol, and marijuana during pregnancy than do nonusers of cocaine. When these differences between the exposure groups are controlled, preliminary analyses indicate there is no significant effect of prenatal cocaine use on infant growth and morphology. CONCLUSIONS: Future research needs to address the effects of prenatal cocaine and/or crack exposure on central nervous system development and on the long-term development of exposed offspring.

Prenatal alcohol exposure: a continuum of effects.

Studies of alcohol consumption, although somewhat inconsistent, have shown a relationship between prenatal alcohol exposure, growth retardation, and morphologic abnormalities. The inconsistency of the observed effects may be a result of differential exposure, exposure at different times during pregnancy, methodologic problems with identification and measurement, or inadequate control for risk factors that covary with alcohol consumption. There have been too few studies to assess accurately the effect of drinking on development beyond the neonatal period. Some studies have found that infants of heavy drinking mothers are growth-retarded and developmentally delayed throughout the preschool ages. These effects seem to be related to prenatal alcohol exposure in a dose-response manner. While these studies await replication, these findings do parallel those reported for children with FAS and children of alcoholic mothers. Laboratory research has also shown that toxic exposures during pregnancy affect the fetus differentially as the exposure dose increases, beginning with behavioral or central nervous system effects, then growth and morphologic effects. FAS patients are affected in all of these domains with cognitive and behavioral problems, growth retardation, and morphologic abnormalities. Children who have been prenatally exposed to moderate levels of alcohol in the MHPCD sample also show deficits in each of these domains, illustrating a continuum of response. Thus, the consequences of heavy drinking seem to represent the more severe end of a continuum of effects seen in the offspring of alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of prenatal substance exposure: altered maturation of visual evoked potentials.

We investigated the effects of prenatal substance use on visual evoked potentials (VEPs). Seventy-four children were tested at birth and 1 month of age with binocular flash VEPs and at 4, 8, and 18 months of age with binocular pattern VEPs. Regressions were run by trimester to assess the independent effects of substance exposure. Variables included in the regression model were alcohol, marijuana, tobacco, other drug use for each trimester, maternal age, education, income, race, marital status, infant sex, birthweight, and Dubowitz score. Changes in specific components of the binocular VEP were both substance- and trimester-specific. First trimester alcohol use was associated with prolonged P1 wave latencies at 1 month of age. Prolonged P1 wave latencies at birth and 18 months were associated with tobacco use during each of the three trimesters, at 1 and 18 months with third trimester marijuana use, and at 1 and 18 months with first trimester other illicit drug use. Although these women were moderate substance users during pregnancy, their offspring exhibited maturational changes in components of the VEP in the absence of neonatal behavioral disturbances.

Maternal and neonatal effects of moderate cocaine use during pregnancy.

Thirty-four women who reported using cocaine during pregnancy were compared to 600 women who reported no cocaine use during pregnancy and none for the year prior to pregnancy. Subjects were participants in a prospective, longitudinal study of prenatal substance use. The sample consisted of young, predominantly single, low-income women attending a public prenatal clinic. Women were interviewed at the end of their first, second and third trimesters regarding cocaine, alcohol, marijuana, tobacco and other drug use. The majority of the cocaine users were light to moderate users who decreased their use during pregnancy. The cocaine group was more likely to be white and to use alcohol, marijuana, tobacco and other illicit drugs more heavily than the comparison group. The cocaine users had more previous fetal losses but did not differ on other obstetrical complications. Infant growth, morphology and behavior were not affected.

Prenatal alcohol, marijuana, and tobacco use: infant mental and motor development.

These data are from a longitudinal study of prenatal alcohol and marijuana use in a low income sample. Half of the women were black and half were white. Women who used alcohol and/or marijuana during their pregnancies were light to moderate users; most decreased or discontinued their use after the first trimester. At the first follow-up phase, which occurred at a median age of 9 months, the children were functioning above average on the Bayley Scales of Infant Development (BSID). Prenatal alcohol and tobacco use did not predict BSID mental or motor scores at this phase. Third trimester marijuana use was associated with decreased BSID mental scores. Age at assessment was the most important predictor at this phase. The second follow-up occurred at a median age of 19 months when the group means for the BSID were lower. Prenatal alcohol and marijuana use did not predict outcome at this phase. Prenatal and current cigarette use were associated with decreased BSID mental scores. Demographic and environmental variables were important predictors at this phase.

Effects of prenatal marijuana exposure on child behavior problems at age 10.

This is a prospective study of the effects of prenatal marijuana exposure on child behavior problems at age 10. The sample consisted of low-income women attending a prenatal clinic. Half of the women were African-American and half were Caucasian. The majority of the women decreased their use of marijuana during pregnancy. The assessments of child behavior problems included the Child Behavior Checklist (CBCL), Teacher's Report Form (TRF), and the Swanson, Noland, and Pelham (SNAP) checklist. Multiple and logistic regressions were employed to analyze the relations between marijuana use and behavior problems of the children, while controlling for the effects of other extraneous variables. Prenatal marijuana use was significantly related to increased hyperactivity, impulsivity, and inattention symptoms as measured by the SNAP, increased delinquency as measured by the CBCL, and increased delinquency and externalizing problems as measured by the TRF. The pathway between prenatal marijuana exposure and delinquency was mediated by the effects of marijuana exposure on inattention symptoms. These findings indicate that prenatal marijuana exposure has an effect on child behavior problems at age 10.

The effects of prenatal cocaine use on neonatal neurobehavioral status.

The effect of prenatal cocaine use on neonatal behavior was examined, using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS), in a prospective study of women attending a prenatal clinic. Women were interviewed at the end of each trimester. Term infants were assessed with the BNBAS at day 2 (N = 165) (mean = 35.6 h) and at day 3 (N = 108) (mean = 60.1 h). Women averaged 25 years of age with 12 years of education; 48% were African-American and 20% were married. Women who used cocaine were more likely to use tobacco, alcohol, and marijuana. Regression analyses, with the Lester et al. (22) clusters as outcomes, were used to control for covariates of cocaine use such as other substance use and sociodemographic characteristics. On day 2, first, second, and third trimester cocaine/crack use were significantly related to poorer autonomic stability, second and third trimester use were related to poorer motor maturity and tone, and first and second trimester use were associated with an increased number of abnormal reflexes. These relationships were not present on day 3. These results may be transient expressions of the effect of prenatal cocaine exposure on central nervous system maturation.

Prenatal cocaine exposure: effects on the development of school-age children.

The offspring of 28 women who reported light to moderate cocaine use during pregnancy were compared with those of 523 women who reported no cocaine use during pregnancy and none for the year prior to pregnancy. Subjects were participants in two prospective, longitudinal studies of prenatal substance use. Women were interviewed during their fourth and seventh months of pregnancy, at delivery, and at 8, 18, 36, and 72 months postpartum regarding cocaine, alcohol, marijuana, tobacco, and other drug use. At 6 years, children underwent physical examination, and their cognitive development, academic achievement, and behavior were assessed. The women in the cocaine group were more likely to be Caucasian and to use more alcohol, marijuana, tobacco, and other illicit drugs than those in the comparison group. When demographic and substance use differences between the groups were controlled, there were no significant effects of prenatal cocaine exposure on the growth, intellectual ability, academic achievement, or teacher-rated classroom behavior of the 6-year-old offspring. Children prenatally exposed to cocaine did show deficits in their ability to sustain attention on a computerized vigilance task.

Prenatal substance exposure: effects on attention and impulsivity of 6-year-olds.

Attention and impulsivity of prenatally substance-exposed 6 year olds were assessed as part of a longitudinal study. Most of the women were light to moderate users of alcohol and marijuana who decreased their use after the first trimester of pregnancy. Tobacco was used by a majority of women and did not change during pregnancy. The women, recruited from a prenatal clinic, were of lower socio-economic status, and over half were African American. Attention and impulsivity were assessed using a Continuous Performance Task. Second and third trimester tobacco exposure and first trimester cocaine use predicted increased omission errors. Second trimester marijuana use predicted more commission errors and fewer omission errors. There were no significant effects of prenatal alcohol exposure. Lower Stanford-Binet Intelligence Scale composite scores, male gender, and an adult male in the household also predicted more errors of commission. Lower SBIS composite scores, younger child age, maternal work/ school status, and higher maternal hostility scores predicted more omission errors. These findings indicate that prenatal substance use has an effect on attentional processes.

Effect of prenatal marijuana exposure on the cognitive development of offspring at age three.

Marijuana is the most commonly used illicit substance among pregnant women. Although there has been substantial concern about the effects of substance use during pregnancy, few studies have assessed the effects of prenatal exposure to marijuana and even fewer have provided longitudinal data on the developmental outcome of offspring. This is a report from a longitudinal study of substance use during pregnancy. The women in the cohort were of lower socioeconomic status, most were single, half were white and half were African-American. Women were interviewed at the fourth and seventh prenatal months, and women and children were assessed at delivery, 8, 18, and 36 months. Pediatric assessment included physical and cognitive development. At each study phase, mothers were interviewed about life style, living situation, current substance use, sociodemographic, and psychological status. Findings are reported on 655 women and children who were assessed at the third year. There were significant negative effects of prenatal marijuana exposure on the performance of 3-year-old children on the Stanford-Binet Intelligence Scale. The effects were associated with exposure during the first and second trimesters of pregnancy. Among the offspring of white women, these effects were moderated by the child's attendance at preschool/day-care at age three.

Prenatal marijuana use: epidemiology, methodologic issues, and infant outcome.

What do we know about marijuana use among women of reproductive age and about the use of marijuana during pregnancy? Marijuana is the most commonly used illicit substance, and after alcohol and tobacco, the most commonly used drug during pregnancy. Women who use marijuana are more likely to be white, younger, and to use other substances. The characteristics of women who use marijuana during early pregnancy are similar, although women who continue to use marijuana throughout pregnancy are somewhat different. These women are less-well educated, of lower social class, much more likely to use other substances, and more likely to be black. We do not know why some women use marijuana while others do not, and why some women discontinue their use during pregnancy while others do not. What do we know about the effects of marijuana use during pregnancy? A number of studies have investigated the relationship between prenatal marijuana exposure and outcome at birth. The results, unfortunately, are equivocal. Prospective studies that have examined women at regular and frequent intervals during pregnancy, in general, have not found a relationship between marijuana use and birthweight (Day NL, Sambamoorthi U, Taylor P, et al: unpublished data, 1990) although some have reported a small effect of marijuana use on birth length (Day NL, Sambamoorthi U, Taylor P, et al: unpublished data, 1990). Other studies, some prospective and some retrospective, have reported correlations between marijuana use during pregnancy and smaller size at birth. Several of these studies, however, failed to control adequately for other illicit drug use while one used marijuana only as a dichotomous variable in the analysis. Therefore, we do not yet know whether there is or is not an effect of marijuana use during pregnancy on intrauterine growth retardation. Only a few studies have reported on growth outside the neonatal period, and these studies have not found a consistent effect of prenatal marijuana exposure. There are, however, too few reports to assume that this is definitive. Several studies reported a relationship between prenatal marijuana use and the gestational age of the infant. As with growth, however, other studies have not corroborated these findings. Similarly, two studies have noted an increase in morphologic abnormalities, although one of these did not have a control group for comparison. Most studies have reported finding no relationship with either minor or major morphologic abnormalities. At birth, investigators have assessed the relationship between prenatal marijuana exposure and neurobehavioral outcome. Again, the results are contradictory.(ABSTRACT TRUNCATED AT 400 WORDS)

A comparison of prenatal drinking in two recent samples of adolescents and adults.

The drinking patterns of 124 pregnant teenagers are described and compared with those of 267 pregnant adults attending the same prenatal clinic in Pittsburgh. Adults had a significantly higher average daily volume of alcohol prior to pregnancy than adolescents, but that higher level was no longer significant during pregnancy. However, the rate of binge drinking during the first trimester was higher in the teenage sample than in the adult sample. Rates of binge drinking and heavy drinking were highest among the white teenage group. Use of marijuana and cocaine/crack decreased precipitously during pregnancy for both teenagers and adults. Tobacco use also decreased among the adults, but increased from 56% to 71% during pregnancy in the teenage sample. Based on our findings, patterns of drinking among adult pregnant women do not generalize to pregnant adolescents. Offspring of white adolescents, in particular, may be at higher risk for intermittent high peak alcohol exposure farther into the pregnancy than are offspring of older women.

Effects of prenatal tobacco exposure on preschoolers' behavior.

This is a longitudinal study of the relationship between prenatal tobacco exposure and the development of behavior problems in 672 children at the age of 3 years. Women from a prenatal clinic were interviewed about substance use at the end of each trimester of their pregnancy and at 3 years postpartum. Children were assessed at the age of 3 years with maternal ratings of behavior problems, activity, and attention. The prevalence of tobacco use was high in this cohort; 54.3% and 52.3% of the women smoked tobacco in the first and third trimesters of pregnancy, respectively. At 3 years postpartum, 61.6% of the women were smokers. There were significant effects of prenatal tobacco exposure on the children's behavior at age 3 years. Increases in scores on the Oppositional Behavior, Immaturity, Emotional Instability, Physical Aggression, and Activity scales and in the total score on the Toddler Behavior Checklist (TBC) were significantly associated with prenatal tobacco exposure. Smoking one pack of tobacco cigarettes per day during the third trimester of pregnancy was associated with an increase of 6 points in the total problem behavior score. Among the subscales of the TBC, tobacco exposure had the largest effect on oppositional behavior. Impulsivity and peer problems were associated with both prenatal and current tobacco exposure. Only current tobacco exposure predicted attention problems. Prenatal tobacco exposure had a significant negative effect on the development of behavior problems among preschoolers.