CENTER ON BEHAVIORAL MEDICINE
ENVIRONMENTAL INTOLERANCES and TOXINSEnvironmental Intolerances and Toxins-Chemical: Research Article
Sood, B., Delaney-Black, V., et al. (2001). Prenatal
Alcohol Exposure and Childhood
Behavior at Age 6 to 7 Years: I. Dose-Response Effect. Pediatrics 2001;108;34.
Objective. Moderate to heavy levels of prenatal alcohol exposure have been associated with alterations in child behavior, but limited data are available on adverse effects after low levels of exposure. The objective of this study was to evaluate the dose-response effect of prenatal alcohol exposure for adverse child behavior outcomes at 6 to 7 years of age.
Methods. Beginning in 1986, women attending the urban university-based maternity clinic were routinely screened at their first prenatal visit for alcohol and drug use by trained research assistants from the Fetal Alcohol Research Center. All women reporting alcohol consumption at conception of at least 0.5 oz absolute alcohol/day and a 5% random sample of lower level drinkers and abstainers were invited to participate to be able to identify the associations between alcohol intake and child development. Maternal alcohol, cigarette, and illicit drug use were prospectively assessed during pregnancy and postnatally. The independent variable in this study, prenatal alcohol exposure, was computed as the average absolute alcohol intake (oz) per day across pregnancy. At each prenatal visit, mothers were interviewed about alcohol use during the previous 2 weeks. Quantities and types of alcohol consumed were converted to fluid ounces of absolute alcohol and averaged across visits to generate a summary measure of alcohol exposure throughout pregnancy. Alcohol was initially used as a dichotomous variable comparing children with no prenatal alcohol exposure to children with any exposure. To evaluate the effects of different levels of exposure, the average absolute alcohol intake was relatively arbitrarily categorized into no, low (>0 but <0.3 fl oz of absolute alcohol/day), and moderate/heavy (>0.3 fl oz of absolute alcohol/day) for the purpose of this study. Six years later, 665 families were contacted. Ninety-four percent agreed to testing. Exclusions included children who missed multiple test appointments, had major congenital malformations (other than fetal alcohol syndrome), possessed an IQ >2 standard deviations from the sample mean, or had incomplete data. The Achenbach Child Behavior Checklist (CBCL) was used to assess child behavior. The CBCL is a parent questionnaire applicable to children ages 4 to 16 years. It is widely used in the clinical assessment of children’s behavior problems and has been extensively used in research. Eight syndrome scales are further grouped into Externalizing or undercontrolled (Aggressive and Delinquent) behavior and internalizing or overcontrolled (Anxious/Depressed, Somatic Complaints, and Withdrawn) behaviors. Three syndromes (Social, Thought, and Attention Problems) fit neither group. Higher scores are associated with more problem behaviors. Research assistants who were trained and blinded to exposure status independently interviewed the child and caretaker. Data were collected on a broad range of control variables known to influence childhood behavior and/or to be associated with prenatal alcohol exposure. These included perinatal factors of maternal age, education, cigarette, cocaine, and other substances of abuse and the gestational age of the baby. Postnatal factors studied included maternal psychopathology, continuing alcohol and drug use, family structure, socioeconomic status, children’s whole blood lead level, and exposure to violence. Data were collected only from black women as there was inadequate representation of other racial groups.
Statistical Analyses. Statistical analyses were performed using the SPSS statistical package. Frequency distribution, cross-tabulation, odds ratio, and x2 tests were used for analyzing categorical data. Continuous data were analyzed using t tests, analyses of variance (ANOVAs) with posthoc tests, and regression analysis. <>
Results. Testing was available for 501 parent–children dyads. Almost one fourth of the women denied alcohol use during pregnancy. Low levels of alcohol use were reported in 63.8% and moderate/heavy use in 13% of pregnancies. Increasing prenatal alcohol exposure was associated with lower birth weight and gestational age, higher lead levels, higher maternal age, and lower education level, prenatal exposure to cocaine and smoking, custody changes, lower socioeconomic status, and paternal drinking and drug use at the time of pregnancy. Children with any prenatal alcohol exposure were more likely to have higher CBCL scores on Externalizing (Aggressive and Delinquent) and Internalizing (Anxious/Depressed and Withdrawn) syndrome scales and the Total Problem Score. The odds ratio of scoring in the clinical range for Delinquent behavior was 3.2 (1.3–7.6) in children with any prenatal exposure to alcohol compared with nonexposed controls. The threshold dose was evaluated with the 3 prenatal alcohol exposure groups. Oneway ANOVA revealed a significant between group difference for Externalizing (Aggressive and Delinquent) and the Total Problem Score. Posthoc tests revealed the between group differences to be significant (no and low-exposure group) for Aggressive and Externalizing behavior suggesting that the adverse effects of prenatal alcohol exposure on child behavior at age 6 to 7 years are evident even at low levels of exposure. For Delinquent and Total Problem behavior, the difference was significant between the no and moderate-heavy exposure group, suggesting a higher threshold for these behaviors. Prenatal alcohol exposure remained a significant predictor of behavior after adjusting for covariates. Although maternal psychopathology was the most important predictor of behavior, gender was also a significant predictor, with boys having higher scores on Externalizing (Delinquent) and Attention Problems. The amount of variance uniquely accounted for by prenatal alcohol exposure ranged between 0.6% to 1.7%.
alcohol consumption even at low levels was adversely related to child
a dose-response relationship was also identified. The effect was
average levels of exposure of as low as 1 drink per week. Although
mean scores for Externalizing and Aggressive behaviors were observed at
levels of prenatal alcohol exposure, effects on Delinquent behavior and
Problem Scores were observed at moderate/heavy levels of exposure.
with any prenatal alcohol exposure were 3.2 times as likely to have
behavior scores in the clinical range compared with nonexposed
relationship between prenatal alcohol exposure and adverse childhood
outcome persisted after controlling for other factors associated with
behavioral outcomes. Clinicians are often asked by pregnant women if
of alcohol intake are acceptable during pregnancy. These data suggest
alcohol during pregnancy remains the best medical advice.
Ashford NA, Miller CS. Chemical Exposures: Low Levels and High Stakes.
2. Davidoff AL, Fogarty L. Psychogenic origins of multiple chemical sensitivities syndrome: a critical review of the research literature. Arch Environ Health 49:316–325 (1994).
3. Kipen HM, Fiedler N. Invited commentary: sensitivities to chemicals—context and implications. Am J Epidemiol 150:13–16 (1999).
4. Neutra RR, Kreutzer R. Reply to “invited commentary: sensitivities to chemicals—context and implications” by Kipen and Fiedler. Am J Epidemiol 150:17 (1999).
S, Gots RE. Chemical Sensitivity: The Truth about Environmental
7. Sparks PJ, Daniell W, Black DW, Kipen HM, Altman LC, Simon GE, Terr AI. Multiple chemical sensitivity syndrome: a clinical perspective. I. Case definition, theories of pathogenesis, and research needs. Occup Med 36(7):718–730 (1994).
8. Meggs WJ. Neurogenic inflammation and sensitivity to environmental chemicals. Environ Health Perspect 101:234–238 (1993).
Bascom R. Multiple chemical sensitivity: a respiratory disorder?
Antelman SM. Time-dependent sensitization in animals: a possible model
multiple chemical sensitivity in humans.
Gilbert ME. The phenomenology of limbic kindling.
Miller CS. Possible models for multiple chemical sensitivity:
and role of the limbic system.
Bell IR. White paper: neuropsychiatric aspects of sensitivity to
chemicals: a neural sensitization model.
Bell IR, Szarek MJ,
16. Cullen MR. The worker with multiple chemical sensitivities: an overview. Occup Med 2:655–661 (1987).
Nova Scotia Department of Health. The
18. Kreutzer R, Neutra RR, Lashuay N. Prevalence of people reporting sensitivities to chemicals in a populationbased survey. Am J Epidemiol 150:1–12 (1999).19. Meggs WJ, Dunn KA, Bloch RM, Goodman PE, Davidoff AL. Prevalence and nature of allergy and chemical sensitivity in a general population. Arch Environ Health 51:275–282 (1996).
20. Kipen HM, Hallman W, Kang H, Fiedler N, Natelson BH. Prevalence of chronic fatigue and chemical sensitivities in Gulf Registry Veterans. Arch Environ Health 54(5):313–318 (1999).
21. Multiple Chemical Sensitivity: A 1999 Consensus. Arch Environ Health 54:147–149 (1999).22. McKeown-Eyssen G, Marshall L, Ross G, Krondl M, Sokoloff E. The
Ministry of Health.
McKeown-Eyssen GE, Sokoloff ER, Jazmaji V,
25. Sharabi Y, Danon YL, Berkenstadt H, Almog S, Mimouni-Bloch A, Zisman A, Dani S, Atsmon J. Survey of symptoms following intake of pyridostigmine during the Persian Gulf war. Isr J Med Sci 27(11–12):656–658 (1991).
26. Friedman A, Kaufer D, Shemer J, Hendler I, Soreq H, Tur-Kaspa I. Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response. Nat Med 2(12):1382–1385 (1996).
H, Stern A, Rotnitzky A, Schlesinger L, Proctor S, Wolfe J. Development
brief questionnaire for screening for multiple chemical sensitivity
28. Davidoff AL, Fogarty L, Keyl PM. Psychiatric inferences from data on psychologic/psychiatric symptoms in multiple chemical sensitivities syndrome. Arch Environ Health 55(3):165–175 (2000).
Doty RL. Olfaction and multiple chemical sensitivity.
30. Fox AR, Sabo BMT, Williams TPW, Joffres MR. Intradermal Testing for Food and Chemical Sensitivity: A Double-Blind Controlled Study. J Allergy Clin Immunol 103:907–911 (1999).31.
32. Thompson GM, Day JH, Evers S, Gerrard JW, McCourtie DR, Woodward WD. Report of the Ad Hoc Committee on Environmental Hpersensitivity Disorders.