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Prenatal exposure to binge drinking and cognitive and behavioral outcomes at age 7 years
American Journal of Obstetrics and Gynecology (2004) 191, 1037–43
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Prenatal exposure to binge drinking and cognitive and behavioral outcomes at age 7 years Beth Nordstrom Bailey, PhD,a,* Virginia Delaney-Black, MD, MPH,b Chandice Y. Covington, PhD, RN,f Joel Ager, PhD,c James Janisse, PhD,c John H. Hannigan, PhD,d,e Robert J. Sokol, MDd Department of Family Medicine, East Tennessee State University, Johnson City, Tenn,a Department of Pediatrics,b Center for Health Care Effectiveness Research,c Department of Obstetrics and Gynecology, School of Medicine,d Department of Psychology,e Wayne State University, Detroit, Mich, and School of Nursing, University of California at Los Angeles, Calif f
KEY WORDS Prenatal alcohol exposure Binge drinking Child outcome
Objective: The goal of this study was to examine differential effects of amount and pattern of prenatal alcohol exposure on child outcome. Study design: Alcohol use was assessed at each prenatal visit, and IQ and behavior were measured at age 7 years. Results: After control for confounders, the amount of exposure was unrelated to IQ score and behavior for O500 black 7-year-old children. However, children who were exposed to binge drinking were 1.7 times more likely to have IQ scores in the mentally retarded range and 2.5 times more likely to have clinically significant levels of delinquent behavior. Conclusion: During prenatal care, clinicians should attend not only to amount but also to the pattern of alcohol intake, because of the elevated risk for cognitive deficits and long-term behavioral abnormality. Ó 2004 Elsevier Inc. All rights reserved.
Prenatal exposure to alcohol has been implicated as the most common cause of mental retardation and the leading preventable cause of birth defects in the United States.1 Exposure has profound effects on children and their families and accounts for significant educational and public health expenditures. Up to 50% of women of Supported by National Institute of Drug Abuse R01 DA08524 (V.D-B.). Presented at the Twenty-Fourth Annual Meeting of the Society for Maternal Fetal Medicine, New Orleans, LA, February 2-7, 2004. * Reprint requests: Beth Nordstrom Bailey, PhD, Department of Family Medicine, James H. Quillen College of Medicine, East Tennessee State University, PO Box 70621, Johnson City, TN 37614. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.05.048
childbearing age consume alcohol; 20% of these women continue to consume alcohol during pregnancy.2 Consequently, the national incidence of fetal alcohol syndrome, which is characterized by specific facial dysmorphologic conditions, growth restriction, mental retardation, and known high levels of prenatal alcohol exposure, is estimated as high as 4.8 occurrences per 1000 births.3 Moreover, fetal alcohol syndrome represents the tip of the iceberg, because many more children who are exposed at lower levels may experience impaired development. Fetal alcohol spectrum disorder, the latest term to encompass all levels of and outcomes associated with prenatal alcohol exposure, affects approximately 1 in 100 births.3
1038 Several domains of development are impacted by prenatal alcohol exposure. In addition to widely described characteristic facial dysmorphology and growth restriction,1 decreased cognitive ability,4,5 and increased behavior problems5,6 into childhood have been associated with prenatal alcohol exposure in many but not all studies.7-9 Additionally, even small amounts of alcohol exposure (1 oz/d) have been linked to significant IQ decrements.10 Lack of evidence of universal cognitive and behavioral consequences from prenatal alcohol exposure may be related to many individual factors that include metabolism, genetic susceptibility, and variation in brain region vulnerability.11 Timing of prenatal alcohol exposure may also play a role.12 Additionally, a pattern of alcohol consumption has been implicated as an important influence. Consuming many drinks per occasion (ie, binge drinking) may be more harmful to the developing fetus than the same amount spread out over several days, because of higher peak blood alcohol content in the first instance.11 However, few human studies have examined the pattern of exposure in relation to child outcomes, because most research on prenatal alcohol exposure includes alcohol use information as an average over time rather than as an inquiry of how much alcohol is consumed per occasion.13 Two large studies, however, do have data for binge patterns of prenatal alcohol exposure. Results from a sample in Seattle, Wash, indicate that binge drinking ( R5 drinks/ occasion) is associated with cognitive deficits and behavior problems at age 7 years.10 No association was found between the amount of prenatal alcohol exposure averaged across pregnancy and child outcomes. Similar findings were reported for infants in Detroit, Mich.14 It appears, then, that the pattern of prenatal alcohol exposure may be associated more highly with negative child outcomes than the total amount of exposure averaged across pregnancy. This may be one reason that results of studies of children with prenatal alcohol exposure vary considerably. Additional research, with sound methods and adequate power, clearly is needed to confirm the limited findings regarding pattern of exposure, findings that could have significant implications for the advice that is given to pregnant women regarding alcohol consumption. The goal of the current study was to examine possible differential effects of the amount of prenatal alcohol exposure averaged across pregnancy and the pattern of such exposure (specifically bingeing) on early school-age cognition and behavior. It was first hypothesized that prenatal exposure to binge drinking, but not overall amount of exposure, would predict lower IQ scores in a sample of 7-year-old, inner-city, black children. Second, we hypothesized that prenatal exposure to binge drinking, but not the overall amount of exposure, would pre-
Bailey et al dict increased levels of behavior problems in this same sample.
Material and methods Subjects All mothers in this study received prenatal care at Wayne State University clinics and participated in a larger institutional review boardeapproved pregnancy study. The pregnancy study enrolled 600C women annually on the basis of a strategy to oversample alcohol-exposed pregnancies. The women who enrolled were interviewed at each prenatal visit, and the infants were evaluated neonatally. Urine was collected at visits and delivery as clinically indicated. Children who were delivered from September 1, 1989, to August 31, 1991, to women who were enrolled in the pregnancy study were eligible for this study. The study sample was limited to the 90% of mothers who were black. Additional exclusions included multiple gestation, major congenital malformations, known positive maternal human immunodeficiency virus status, and moving out of the Detroit area. At follow-up 6 to 7 years later, families were sought intensively by telephone, mail, or home visit to the last known address. Files of Detroit-based hospitals and primary care services were searched for updated contact information. Additionally, children were sought through private and public school systems. Of the births to women who were enrolled at the University maternity center during the study period, 1028 births initially were deemed eligible to participate. Exclusions included births to women who were known to be positive for human immunodeficiency virus, not black, multiple births, and repeat deliveries to women who were enrolled. Additional exclusions included children with multiple malformations. From the 1028 eligible births, 357 children had moved out of the area, had been adopted, or could not be located after extensive searching (presumed to have moved away). An additional 6 children were deceased. The remaining 665 families represented the potential study sample.
Procedures Children and primary caretakers were evaluated after the child’s expected entry into the first grade. Testing in our research facility included IQ assessment and other measures that will be described later. Research assistants who were blinded to exposure status interviewed each child and mother independently. Another assistant collected teacher data. Mailings went to each teacher, and, if the questionnaires were not returned, an appointment was made to meet with the teacher.
Bailey et al
Measures Prenatal alcohol exposure Women were interviewed at all prenatal visits (timing and number varied by subject) regarding alcohol use. Recall of previous 2-week consumption was linked to specific drinking habits (including time of day, day of week) and included information on binge drinking. Intake was converted to ounces of absolute alcohol per day based on type of alcoholic beverage. Two exposure variables were then created: the amount of exposure (ounces of absolute alcohol/day, averaged across pregnancy) and the dichotomous pattern of exposure (positive, if the self-report was of R5 drinks/ occasion at least once every 2 weeks during pregnancy). Other prenatal exposures A standardized research interview was conducted during pregnancy to elicit cocaine, heroin, marijuana, and opiate use. During pregnancy and at delivery, urine was also tested for drugs when evidence of past or current drug or alcohol use existed. Women were considered to have specific drug exposure for any of the following reasons: a history of use of the drug from interviews that were conducted throughout pregnancy, information from prenatal or neonatal records, positive maternal urine at any time during pregnancy, or positive maternal or infant urine at delivery. At the follow-up, an additional 13 women retrospectively admitted, for the first time, to using drugs during pregnancy. Their children were also considered drug exposed. Prenatal tobacco exposure was calculated from multiple maternal pregnancy reports of the number of cigarettes that had been smoked.
1039 significant; scores !73 were considered in the normal range. Control variables Pregnancy and neonatal data were available, and included information on other prenatal exposures by previously detailed methods. Laboratory testing included demographics, family drug and alcohol use, caregiver psychopathology,16 family socioeconomic status, maternal verbal IQ,17 quality of home environment (laboratory HOME assessment),18 whole blood lead level, and community violence exposure.19
Statistical analyses All variables were checked for normality violations, and 4 significant positive on verbal IQ score outliers were identified on the basis of a 3 standard deviation criterion. These outliers were winsorized by recoding them to 122 (ie, 3 SD greater than a mean of 80), and this variable was used in subsequent analyses. Adequate power (>.80) existed to identify small-to-moderate effect sizes in outcomes. Confounder variables were those variables that correlated (P ! .10) with exposure variables or outcome(s). Confounders were entered stepwise into final regression equations and followed by forced entry of prenatal exposure variables. Prenatal marijuana exposure was not included because of high correspondence with alcohol exposure and nonsignificant relations with outcomes. Similarly, cocaine was the only illicit drug exposure variable that was entered as a confounder because of low incidence and significant overlap with cocaine exposure of the other drugs.
Results Wechsler preschool and primary scales of intelligenceerevised (WPPSI) This well-validated measure was used to assess child intelligence. The WPPSI consists of multiple scales that are grouped to provide total scores for both verbal and performance IQ. Achenbach teacher report form15 This widely used self-report instrument was utilized to assess child behavior problems. The Achenbach Teacher Report Form provides a total problem score and 8 syndrome scales. Of interest to this project were 2 externalizing behavior syndromes that indicated actingout aggressive behavior and delinquent behavior. Raw scores for aggressive and delinquent behavior scales were used in the analyses, except for those analyses that addressed clinical significance and relied on grouped standardized scores (ie, t-scores). A cutpoint of 73 was used on the basis of recommended cut-offs. T-scores of R73 were considered clinically
Sample Of the 665 eligible child-parent dyads, 94% of the families (626 families) agreed to participate; however, 40 of the families (6%) missed multiple appointments. These 40 families and those families with significant missing data (n = 30; 4%) were eliminated from further analysis. The remaining sample consisted of 556 families (84% retention rate). Although teacher compliance was high (>90%), this missing data reduced the sample for behavioral outcome analyses to 499. The children, all of whom were black, ranged in age from 5.9 to 7.9 years (mean = 6.9 years). Women with frequent binge drinking had multiple risk factors (Table III). Bingeing mothers were older and used more cocaine and cigarettes during pregnancy than did the other mothers. Additionally, although bingeexposed children were significantly smaller at birth, gestational duration was not significantly shorter. At follow-up, binge-exposed children were less likely to be
1040 Table I status
Bailey et al Sample characteristics by alcohol exposure group
Background characteristic Infant Birth weight (g)y Gestational age (wk)y Mother Cigarettes during pregnancy (n/d)y Marijuana during pregnancy (%) Cocaine during pregnancy (%) Age at child’s birth (y)y Family at follow-up visit Biologic mother is primary caretaker (%) Marital status of caretaker (% married) Years of caretaker educationy
No binge drinking exposure (n = 481)
Binge drinking exposure* (n = 56)
P value
3021 G 622 38.7 G 2.6
2717 G 634 37.9 G 3.7
.001 NS
7.6 G 9.2
13.8 G 10.8
!.001
35
44
NS
40
67
!.001
25.4 G 6.5
27.8 G 5.2
.009
85
65
!.001
27
21
NS
11.2 G 2.6
11.0 G 2.3
NS
NS, Not significant. * Binge drinking was defined as R 5 drinks per occasion at least once every 2 weeks during pregnancy. y Data given as mean G SD.
in the care of their mothers. There was no difference between the groups for caregiver education status, marital status, or income.
Bivariate and multivariate analyses: IQ As can be seen in Table IV, the amount of prenatal alcohol exposure was not significantly related to verbal or performance IQ. The pattern of exposure was unrelated to performance IQ but was related highly to verbal IQ. Children who were exposed to binge drinking prenatally scored 6 points (approximately one-half SD) lower on verbal IQ, compared with the other children (75 vs 81; t (535) = 2.88; P ! .01). To control for confounding factors (listed in Tables III and IV footnotes), regression analyses were calculated that predicted verbal IQ score from amount and pattern of prenatal alcohol exposure (Table I). After control for significant confounders (quality of home environment, socioeconomic status, child violence exposure), the amount of exposure remained unrelated to child verbal IQ. However, after control for confound-
Table II
Bivariate correlations
Verbal IQ Performance IQ Aggressive behavior Delinquent behavior
Amount of prenatal alcohol exposure*
Pattern of prenatal alcohol exposurey
rz
P value
rz
P value
.07 .03
.09 .49
.12 .02
.00 .61
.05
.24
.07
.13
.10
.02
.12
.01
* Ounces of absolute alcohol per day, averaged across pregnancy. y Pattern considered positive if R 5 drinks were consumed per occasion at least once every 2 weeks during pregnancy. z Pearson correlations.
ing, which included other prenatal exposures, the pattern of alcohol exposure remained significantly related to verbal IQ. To determine clinical significance of the findings, verbal IQ scores were grouped on the basis of standard criteria for mental retardation (70C [normal IQ score] and !70 [subnormal IQ score]). Children who were exposed to R 5 drinks per occasion at least once every 2 weeks were 1.7 times more likely than those children who were exposed to lesser amounts to have subnormal verbal IQ scores (41% vs 24%; c2 (1) = 7.52; P ! .01).
Bivariate and multivariate analyses: behavior As presented in Table III, neither amount nor pattern of prenatal alcohol exposure was related significantly to aggressive behavior. However, both exposure variables were related to delinquent behavior. Children who were exposed to binge drinking prenatally scored a full onehalf standard deviation higher on delinquent behavior problems compared with the remaining children (3.3 vs 2.2; t (497) = e2.70; P ! .01). Regression analyses, which were controlled for confounding, were calculated to predict delinquent behavior from amount and pattern of prenatal alcohol exposure (Table II [confounders listed in footnote]). After control for significant confounders (quality of home environment, child violence exposure), the amount of prenatal alcohol exposure was not related significantly to delinquent behavior. However, the pattern of alcohol exposure remained significantly related to delinquent behavior problems after control for confounding. To determine clinical significance of the findings, delinquent behavior scores were grouped on the basis of Achenbach’s criteria for clinical significance. Children who were exposed to R 5 drinks per occasion at least once every 2 weeks were 2.5 times more likely than those children who were exposed to lesser amounts to have
Bailey et al Table III
1041 Stepwise regression results for verbal IQ
Exposure Amount of alcohol exposurey Quality of home environment Family socioeconomic status Child violence exposure Prenatal exposures Cigarettes Cocaine Amount of alcohol Pattern of alcohol exposurez Quality of home environment Family socioeconomic status Child violence exposure Prenatal exposures Cigarettes Cocaine Pattern of alcohol
R
2
R change
t*
Table IV P value
.28
.080
6.69
!.001
.33
.023
4.02
!.001
.36
.020
3.46
.001
.39
.023 1.94 2.40 1.67
.053 .017 .100
.29
.081
6.72
!.001
.33
.028
3.99
!.001
.36
.020
3.43
.001
.40
.028 1.99 2.34 2.47
.047 .020 .014
Significant covariates included child age, gender, lead level, violence exposure, maternal verbal IQ, psychopathology, depression, age, socioeconomic status, custody changes, current alcohol exposure, number of children in home, and quality of home environment. Additional covariates (nonsignificant relations with both prenatal alcohol and outcomes) that were considered included child Apgar scores, number of hospitalizations, medical diagnoses, and preschool attendance, number of prenatal visits, pregnancy hypertension, pregnancy diabetes mellitus, family income, caretaker marital and employment status, protective services involvement, and paternal involvement. * On final step, with all variables entered. y Absolute ounces of alcohol per day, averaged across pregnancy. z Pattern considered positive if R 5 drinks were consumed per occasion at least once every 2 weeks during pregnancy.
clinically significant levels of delinquent behavior (17% vs 7%; c2 (1) = 7.75; P ! .01).
Comment Prenatal alcohol exposure was significantly related to both decreased IQ score and increased behavior problems in this large sample of black first grade students. Children who were exposed to binge drinking prenatally, regardless of the amount of overall pregnancy exposure, had significantly lower verbal IQ scores and significantly higher levels of teacher-reported delinquent behavior compared with the remaining children, even after control for other prenatal exposures and postnatal environmental factors (including current alcohol exposure, maternal IQ, quality of home environment, socio-
Stepwise regression results for delinquent behavior
Exposure Amount of alcohol exposurey Quality of home environment Child violence exposure Prenatal exposure Cigarettes Cocaine Amount of alcohol Pattern of alcohol exposurez Quality of home environment Child violence exposure Prenatal exposure Cigarettes Cocaine Pattern of alcohol
R
R2 change
.15
t*
P value
.023
3.96
!.001
.20
.016
2.84
.005
.22
.008 .71 .66 1.68
.480 .510 .100
.15
.024
3.38
.001
.20
.016
2.81
.005
.23
.013 .70 .80 2.26
.485 .427 .024
Significant covariates included child age, gender, lead level, violence exposure, maternal verbal IQ, psychopathology, depression, age, socioeconomic status, custody changes, current alcohol exposure, number of children in home, and quality of home environment. Additional covariates (nonsignificant relations with both prenatal alcohol and outcomes) that were considered included child Apgar scores, number of hospitalizations, medical diagnoses, and preschool attendance, number of prenatal visits, pregnancy hypertension, pregnancy diabetes mellitus, family income, caretaker marital and employment status, protective services involvement, and paternal involvement. * On final step, with all variables entered. y Absolute ounces of alcohol per day, averaged across pregnancy. z Pattern considered positive if R 5 drinks were consumed per occasion at least once every 2 weeks during pregnancy.
economic status, and violence exposure). Thus, the pattern of prenatal alcohol exposure was an even more important determinant of outcomes than volume in this large-scale prospective study. Results of the current study support the findings of other researchers who suggest that exposure to binge drinking has more deleterious consequences than the overall amount of exposure to alcohol during pregnancy.10,14 Binge drinking, which produces higher blood alcohol content, produces a higher threshold of exposure and exposes the fetus to alcohol for a longer period of time, both of which are likely to have a more profound effect on developing structures.11 Animal studies appear to support this contention. Rats that are exposed to bingelike prenatal alcohol exposure have more severe brain injury than rats that are exposed to the same amount of alcohol over a longer period.20 Similar studies have reported brain damage after a single instance of binge exposure.21 Thus, findings of the current investigation
1042 demonstrate that simply looking at the overall amount of exposure may obscure important prenatal alcohol exposure effects. This may be one reason why several researchers have failed to find an effect of prenatal alcohol exposure on child cognitive and behavioral outcomes.7-9 An interesting finding of the current study is the lack of an association between binge drinking exposure and performance IQ. Like other researchers, we demonstrated a link between prenatal alcohol exposure (in our case binge drinking exposure) and verbal IQ.4,10 However, exposure and performance IQ were not related. This finding may be due to the characteristics of our sample, which include significant variance in performance IQ scores attributable to confounding variables. Still, a few other studies have reported similar findings22 and posit how this potential difference may indicate specific, rather than global, effects of prenatal alcohol exposure on cognition.23 The current study has many strengths, which include a large sample size, prospectively collected prenatal alcohol exposure that includes the measurement of binge drinking, the assessment of the children 7 years after birth, and the inclusion of many confounders. However, the study could be improved by including additional measures of cognition, as the effects of prenatal alcohol exposure may be quite specific. In addition, the current study is limited in generalizability as it excluded women with no prenatal care and included only black families who lived in the Detroit area. Despite these limitations, these results provide further evidence, from a study with significant statistical power and sound methodology, that pattern of prenatal alcohol exposure plays a significant role in child outcomes. Further investigation is warranted to replicate these findings and to include more specific outcome measures. Finally, it is important to recognize the implications for prenatal care. Pregnant women who drink heavily are routinely advised of the potential consequences and encouraged strongly to cease or at least to cut back intake. However, if cutting back involves drinking less often, but still consuming large amounts when intake occurs, offspring may not experience improved outcomes. Understanding the consequences of prenatal exposure to binge drinking is especially important because surveys indicate that women of childbearing age who consume alcohol are more likely to binge than drink in a chronic heavy pattern.24 Clinicians should continue to advise against drinking any alcohol during pregnancy and should emphasize that the amount of alcohol that is consumed per occasion may be a more critical factor than the overall number of drinks that are consumed per week. Such understanding and emphasis could go a long way toward decreasing the severity of associated outcomes and the number of children who are born with fetal alcohol syndrome and fetal alcohol spectrum disorder.
Bailey et al
References 1. Abel EL, Sokol RJ. Incidence of fetal alcohol syndrome and economic impact of FAS-related anomalies. Drug Alcohol Depend 1987;19:51-70. 2. Alcohol consumption among pregnant and child-bearing age women: United States, 1991-1995. MMWR Morb Mortal Wkly Res 1997;46:346-50. 3. Sampson PD, Streissguth AP, Bookstein FL. Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology 1997;56:317-26. 4. Mattson SN, Riley EP, Gramling L, Delis DS, Jones KL. Heavy prenatal alcohol exposure with or without physical features of fetal alcohol syndrome leads to IQ deficits. J Pediatr 1997;131: 718-21. 5. Olson HC, Streissguth AP, Sampson PD, Barr HM, Bookstein FL, Thiede K. Association of prenatal alcohol exposure with behavioral and learning problems in early adolescence. J Am Acad Child Adolesc Psychiatry 1997;36:1187-94. 6. Mattson SN, Riley EP. Parent ratings of behavior in children with heavy prenatal alcohol exposure and IQ-matched controls. Alcohol Clin Exp Res 2000;24:226-31. 7. Fried PA, O’Connell CM, Watkinson B. 60- and 70- month followup of children prenatally exposed to marijuana, cigarettes, and alcohol: cognitive and language assessment. J Dev Behav Pediatr 1992;13:383-91. 8. Richardson GA, Day NL, Goldschmidt L. Prenatal alcohol, marijuana, and tobacco use: infant mental and motor development. Neurotoxicol Teratol 1995;17:479-87. 9. Brown RT, Coles CD, Smith IE, Platzman KA, Silverstein J, Erickson S, et al. Effects of prenatal alcohol exposure at school age: II, attention and behavior. Neurotoxical Teratol 1991;13: 369-76. 10. Streissguth AP, Barr HM, Sampson PD. Moderate prenatal alcohol exposure: effects on child IQ and learning problems at age 712; years. Alcohol Clin Exp Res 1990;25:3-11. 11. Maier SE, West JR. Drinking patterns of alcohol-related birth defects. Alcohol Res Health 2001;25:168-74. 12. Goldschmidt L, Richardson GA, Stoffer DS, Geva D, Day NL. Prenatal alcohol exposure and academic achievement at age six: a non-linear fit. Alcohol Clin Exp Res 1996;20:763-70. 13. Gladstone J, Nulman I, Koren G. Reproductive risks of binge drinking during pregnancy. Reproductive Toxicol Rev 1996;10: 3-13. 14. Jacobson JL, Jacobson SW, Sokol RJ, Ager JW. Relation of maternal age and pattern of pregnancy drinking to functionally significant cognitive deficit in infancy. Alcohol Clin Exp Res 1998;22:345-51. 15. Achenbach TM. Manual for the teacher report form/4e18 and 1991 profile. Burlington (VT): University of Vermont; 1991. 16. Derogatis LR, Lipman RS, Covi L. SCl-90: an outpatient psychiatric rating scale, preliminary report. Psychopharmacol Bull 1973;1:13-28. 17. Dunn LM, Dunn LM. Peabody picture vocabulary test-revised. Circle Pines (MN): American Guidance Service; 1981. 18. Caldwell BM, Bradley RH. Home observation for measurement of the environment. Little Rock (AR): University of Arkansas; 1979. 19. Richters JE, Martinez P. Things I have seen and heard: a structured interview for assessing young children’s violence exposure. Washington (DC): National Institute of Mental Health; 1990. 20. Bonthius DJ, West JR. Blood alcohol concentration and microencephaly: a dose response study in the neonatal rat. Teratology 1988;37:223-31. 21. Goodlett CR, Eilers AT. Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: a stereological study of
Bailey et al temporal windows and vulnerability. Alcohol Clin Exp Res 1997;21:738-44. 22. Streissguth AP, Aase JM, Clarren SK, Randels SP, LaDue RA, Smith DF. Fetal alcohol syndrome in adolescents and adults. JAMA 1991;265:1961-7. 23. Don A, Rourke BP. Fetal alcohol syndrome. In: Rourke BP, editor. Syndrome of nonverbal learning disabilities: neurodevelop-
1043 mental manifestations. New York: Guilford Press; 1995.;265: p. 5-32. 24. Wechsler H, Lee JE, Kuo M, Seibring M, Nelson TF, Lee H. Trend in college binge drinking during a period of increased prevention efforts: findings from 4 Harvard School of Public Health College alcohol surveys. J Am Coll Health 2002; 50:203-17.
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Prenatal exposure to binge drinking and cognitive and behavioral outcomes at age 7 years Beth Nordstrom Bailey, PhD,a,* Virginia Delaney-Black, MD, MPH,b Chandice Y. Covington, PhD, RN,f Joel Ager, PhD,c James Janisse, PhD,c John H. Hannigan, PhD,d,e Robert J. Sokol, MDd Department of Family Medicine, East Tennessee State University, Johnson City, Tenn,a Department of Pediatrics,b Center for Health Care Effectiveness Research,c Department of Obstetrics and Gynecology, School of Medicine,d Department of Psychology,e Wayne State University, Detroit, Mich, and School of Nursing, University of California at Los Angeles, Calif f
KEY WORDS Prenatal alcohol exposure Binge drinking Child outcome
Objective: The goal of this study was to examine differential effects of amount and pattern of prenatal alcohol exposure on child outcome. Study design: Alcohol use was assessed at each prenatal visit, and IQ and behavior were measured at age 7 years. Results: After control for confounders, the amount of exposure was unrelated to IQ score and behavior for O500 black 7-year-old children. However, children who were exposed to binge drinking were 1.7 times more likely to have IQ scores in the mentally retarded range and 2.5 times more likely to have clinically significant levels of delinquent behavior. Conclusion: During prenatal care, clinicians should attend not only to amount but also to the pattern of alcohol intake, because of the elevated risk for cognitive deficits and long-term behavioral abnormality. Ó 2004 Elsevier Inc. All rights reserved.
Prenatal exposure to alcohol has been implicated as the most common cause of mental retardation and the leading preventable cause of birth defects in the United States.1 Exposure has profound effects on children and their families and accounts for significant educational and public health expenditures. Up to 50% of women of Supported by National Institute of Drug Abuse R01 DA08524 (V.D-B.). Presented at the Twenty-Fourth Annual Meeting of the Society for Maternal Fetal Medicine, New Orleans, LA, February 2-7, 2004. * Reprint requests: Beth Nordstrom Bailey, PhD, Department of Family Medicine, James H. Quillen College of Medicine, East Tennessee State University, PO Box 70621, Johnson City, TN 37614. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.05.048
childbearing age consume alcohol; 20% of these women continue to consume alcohol during pregnancy.2 Consequently, the national incidence of fetal alcohol syndrome, which is characterized by specific facial dysmorphologic conditions, growth restriction, mental retardation, and known high levels of prenatal alcohol exposure, is estimated as high as 4.8 occurrences per 1000 births.3 Moreover, fetal alcohol syndrome represents the tip of the iceberg, because many more children who are exposed at lower levels may experience impaired development. Fetal alcohol spectrum disorder, the latest term to encompass all levels of and outcomes associated with prenatal alcohol exposure, affects approximately 1 in 100 births.3
1038 Several domains of development are impacted by prenatal alcohol exposure. In addition to widely described characteristic facial dysmorphology and growth restriction,1 decreased cognitive ability,4,5 and increased behavior problems5,6 into childhood have been associated with prenatal alcohol exposure in many but not all studies.7-9 Additionally, even small amounts of alcohol exposure (1 oz/d) have been linked to significant IQ decrements.10 Lack of evidence of universal cognitive and behavioral consequences from prenatal alcohol exposure may be related to many individual factors that include metabolism, genetic susceptibility, and variation in brain region vulnerability.11 Timing of prenatal alcohol exposure may also play a role.12 Additionally, a pattern of alcohol consumption has been implicated as an important influence. Consuming many drinks per occasion (ie, binge drinking) may be more harmful to the developing fetus than the same amount spread out over several days, because of higher peak blood alcohol content in the first instance.11 However, few human studies have examined the pattern of exposure in relation to child outcomes, because most research on prenatal alcohol exposure includes alcohol use information as an average over time rather than as an inquiry of how much alcohol is consumed per occasion.13 Two large studies, however, do have data for binge patterns of prenatal alcohol exposure. Results from a sample in Seattle, Wash, indicate that binge drinking ( R5 drinks/ occasion) is associated with cognitive deficits and behavior problems at age 7 years.10 No association was found between the amount of prenatal alcohol exposure averaged across pregnancy and child outcomes. Similar findings were reported for infants in Detroit, Mich.14 It appears, then, that the pattern of prenatal alcohol exposure may be associated more highly with negative child outcomes than the total amount of exposure averaged across pregnancy. This may be one reason that results of studies of children with prenatal alcohol exposure vary considerably. Additional research, with sound methods and adequate power, clearly is needed to confirm the limited findings regarding pattern of exposure, findings that could have significant implications for the advice that is given to pregnant women regarding alcohol consumption. The goal of the current study was to examine possible differential effects of the amount of prenatal alcohol exposure averaged across pregnancy and the pattern of such exposure (specifically bingeing) on early school-age cognition and behavior. It was first hypothesized that prenatal exposure to binge drinking, but not overall amount of exposure, would predict lower IQ scores in a sample of 7-year-old, inner-city, black children. Second, we hypothesized that prenatal exposure to binge drinking, but not the overall amount of exposure, would pre-
Bailey et al dict increased levels of behavior problems in this same sample.
Material and methods Subjects All mothers in this study received prenatal care at Wayne State University clinics and participated in a larger institutional review boardeapproved pregnancy study. The pregnancy study enrolled 600C women annually on the basis of a strategy to oversample alcohol-exposed pregnancies. The women who enrolled were interviewed at each prenatal visit, and the infants were evaluated neonatally. Urine was collected at visits and delivery as clinically indicated. Children who were delivered from September 1, 1989, to August 31, 1991, to women who were enrolled in the pregnancy study were eligible for this study. The study sample was limited to the 90% of mothers who were black. Additional exclusions included multiple gestation, major congenital malformations, known positive maternal human immunodeficiency virus status, and moving out of the Detroit area. At follow-up 6 to 7 years later, families were sought intensively by telephone, mail, or home visit to the last known address. Files of Detroit-based hospitals and primary care services were searched for updated contact information. Additionally, children were sought through private and public school systems. Of the births to women who were enrolled at the University maternity center during the study period, 1028 births initially were deemed eligible to participate. Exclusions included births to women who were known to be positive for human immunodeficiency virus, not black, multiple births, and repeat deliveries to women who were enrolled. Additional exclusions included children with multiple malformations. From the 1028 eligible births, 357 children had moved out of the area, had been adopted, or could not be located after extensive searching (presumed to have moved away). An additional 6 children were deceased. The remaining 665 families represented the potential study sample.
Procedures Children and primary caretakers were evaluated after the child’s expected entry into the first grade. Testing in our research facility included IQ assessment and other measures that will be described later. Research assistants who were blinded to exposure status interviewed each child and mother independently. Another assistant collected teacher data. Mailings went to each teacher, and, if the questionnaires were not returned, an appointment was made to meet with the teacher.
Bailey et al
Measures Prenatal alcohol exposure Women were interviewed at all prenatal visits (timing and number varied by subject) regarding alcohol use. Recall of previous 2-week consumption was linked to specific drinking habits (including time of day, day of week) and included information on binge drinking. Intake was converted to ounces of absolute alcohol per day based on type of alcoholic beverage. Two exposure variables were then created: the amount of exposure (ounces of absolute alcohol/day, averaged across pregnancy) and the dichotomous pattern of exposure (positive, if the self-report was of R5 drinks/ occasion at least once every 2 weeks during pregnancy). Other prenatal exposures A standardized research interview was conducted during pregnancy to elicit cocaine, heroin, marijuana, and opiate use. During pregnancy and at delivery, urine was also tested for drugs when evidence of past or current drug or alcohol use existed. Women were considered to have specific drug exposure for any of the following reasons: a history of use of the drug from interviews that were conducted throughout pregnancy, information from prenatal or neonatal records, positive maternal urine at any time during pregnancy, or positive maternal or infant urine at delivery. At the follow-up, an additional 13 women retrospectively admitted, for the first time, to using drugs during pregnancy. Their children were also considered drug exposed. Prenatal tobacco exposure was calculated from multiple maternal pregnancy reports of the number of cigarettes that had been smoked.
1039 significant; scores !73 were considered in the normal range. Control variables Pregnancy and neonatal data were available, and included information on other prenatal exposures by previously detailed methods. Laboratory testing included demographics, family drug and alcohol use, caregiver psychopathology,16 family socioeconomic status, maternal verbal IQ,17 quality of home environment (laboratory HOME assessment),18 whole blood lead level, and community violence exposure.19
Statistical analyses All variables were checked for normality violations, and 4 significant positive on verbal IQ score outliers were identified on the basis of a 3 standard deviation criterion. These outliers were winsorized by recoding them to 122 (ie, 3 SD greater than a mean of 80), and this variable was used in subsequent analyses. Adequate power (>.80) existed to identify small-to-moderate effect sizes in outcomes. Confounder variables were those variables that correlated (P ! .10) with exposure variables or outcome(s). Confounders were entered stepwise into final regression equations and followed by forced entry of prenatal exposure variables. Prenatal marijuana exposure was not included because of high correspondence with alcohol exposure and nonsignificant relations with outcomes. Similarly, cocaine was the only illicit drug exposure variable that was entered as a confounder because of low incidence and significant overlap with cocaine exposure of the other drugs.
Results Wechsler preschool and primary scales of intelligenceerevised (WPPSI) This well-validated measure was used to assess child intelligence. The WPPSI consists of multiple scales that are grouped to provide total scores for both verbal and performance IQ. Achenbach teacher report form15 This widely used self-report instrument was utilized to assess child behavior problems. The Achenbach Teacher Report Form provides a total problem score and 8 syndrome scales. Of interest to this project were 2 externalizing behavior syndromes that indicated actingout aggressive behavior and delinquent behavior. Raw scores for aggressive and delinquent behavior scales were used in the analyses, except for those analyses that addressed clinical significance and relied on grouped standardized scores (ie, t-scores). A cutpoint of 73 was used on the basis of recommended cut-offs. T-scores of R73 were considered clinically
Sample Of the 665 eligible child-parent dyads, 94% of the families (626 families) agreed to participate; however, 40 of the families (6%) missed multiple appointments. These 40 families and those families with significant missing data (n = 30; 4%) were eliminated from further analysis. The remaining sample consisted of 556 families (84% retention rate). Although teacher compliance was high (>90%), this missing data reduced the sample for behavioral outcome analyses to 499. The children, all of whom were black, ranged in age from 5.9 to 7.9 years (mean = 6.9 years). Women with frequent binge drinking had multiple risk factors (Table III). Bingeing mothers were older and used more cocaine and cigarettes during pregnancy than did the other mothers. Additionally, although bingeexposed children were significantly smaller at birth, gestational duration was not significantly shorter. At follow-up, binge-exposed children were less likely to be
1040 Table I status
Bailey et al Sample characteristics by alcohol exposure group
Background characteristic Infant Birth weight (g)y Gestational age (wk)y Mother Cigarettes during pregnancy (n/d)y Marijuana during pregnancy (%) Cocaine during pregnancy (%) Age at child’s birth (y)y Family at follow-up visit Biologic mother is primary caretaker (%) Marital status of caretaker (% married) Years of caretaker educationy
No binge drinking exposure (n = 481)
Binge drinking exposure* (n = 56)
P value
3021 G 622 38.7 G 2.6
2717 G 634 37.9 G 3.7
.001 NS
7.6 G 9.2
13.8 G 10.8
!.001
35
44
NS
40
67
!.001
25.4 G 6.5
27.8 G 5.2
.009
85
65
!.001
27
21
NS
11.2 G 2.6
11.0 G 2.3
NS
NS, Not significant. * Binge drinking was defined as R 5 drinks per occasion at least once every 2 weeks during pregnancy. y Data given as mean G SD.
in the care of their mothers. There was no difference between the groups for caregiver education status, marital status, or income.
Bivariate and multivariate analyses: IQ As can be seen in Table IV, the amount of prenatal alcohol exposure was not significantly related to verbal or performance IQ. The pattern of exposure was unrelated to performance IQ but was related highly to verbal IQ. Children who were exposed to binge drinking prenatally scored 6 points (approximately one-half SD) lower on verbal IQ, compared with the other children (75 vs 81; t (535) = 2.88; P ! .01). To control for confounding factors (listed in Tables III and IV footnotes), regression analyses were calculated that predicted verbal IQ score from amount and pattern of prenatal alcohol exposure (Table I). After control for significant confounders (quality of home environment, socioeconomic status, child violence exposure), the amount of exposure remained unrelated to child verbal IQ. However, after control for confound-
Table II
Bivariate correlations
Verbal IQ Performance IQ Aggressive behavior Delinquent behavior
Amount of prenatal alcohol exposure*
Pattern of prenatal alcohol exposurey
rz
P value
rz
P value
.07 .03
.09 .49
.12 .02
.00 .61
.05
.24
.07
.13
.10
.02
.12
.01
* Ounces of absolute alcohol per day, averaged across pregnancy. y Pattern considered positive if R 5 drinks were consumed per occasion at least once every 2 weeks during pregnancy. z Pearson correlations.
ing, which included other prenatal exposures, the pattern of alcohol exposure remained significantly related to verbal IQ. To determine clinical significance of the findings, verbal IQ scores were grouped on the basis of standard criteria for mental retardation (70C [normal IQ score] and !70 [subnormal IQ score]). Children who were exposed to R 5 drinks per occasion at least once every 2 weeks were 1.7 times more likely than those children who were exposed to lesser amounts to have subnormal verbal IQ scores (41% vs 24%; c2 (1) = 7.52; P ! .01).
Bivariate and multivariate analyses: behavior As presented in Table III, neither amount nor pattern of prenatal alcohol exposure was related significantly to aggressive behavior. However, both exposure variables were related to delinquent behavior. Children who were exposed to binge drinking prenatally scored a full onehalf standard deviation higher on delinquent behavior problems compared with the remaining children (3.3 vs 2.2; t (497) = e2.70; P ! .01). Regression analyses, which were controlled for confounding, were calculated to predict delinquent behavior from amount and pattern of prenatal alcohol exposure (Table II [confounders listed in footnote]). After control for significant confounders (quality of home environment, child violence exposure), the amount of prenatal alcohol exposure was not related significantly to delinquent behavior. However, the pattern of alcohol exposure remained significantly related to delinquent behavior problems after control for confounding. To determine clinical significance of the findings, delinquent behavior scores were grouped on the basis of Achenbach’s criteria for clinical significance. Children who were exposed to R 5 drinks per occasion at least once every 2 weeks were 2.5 times more likely than those children who were exposed to lesser amounts to have
Bailey et al Table III
1041 Stepwise regression results for verbal IQ
Exposure Amount of alcohol exposurey Quality of home environment Family socioeconomic status Child violence exposure Prenatal exposures Cigarettes Cocaine Amount of alcohol Pattern of alcohol exposurez Quality of home environment Family socioeconomic status Child violence exposure Prenatal exposures Cigarettes Cocaine Pattern of alcohol
R
2
R change
t*
Table IV P value
.28
.080
6.69
!.001
.33
.023
4.02
!.001
.36
.020
3.46
.001
.39
.023 1.94 2.40 1.67
.053 .017 .100
.29
.081
6.72
!.001
.33
.028
3.99
!.001
.36
.020
3.43
.001
.40
.028 1.99 2.34 2.47
.047 .020 .014
Significant covariates included child age, gender, lead level, violence exposure, maternal verbal IQ, psychopathology, depression, age, socioeconomic status, custody changes, current alcohol exposure, number of children in home, and quality of home environment. Additional covariates (nonsignificant relations with both prenatal alcohol and outcomes) that were considered included child Apgar scores, number of hospitalizations, medical diagnoses, and preschool attendance, number of prenatal visits, pregnancy hypertension, pregnancy diabetes mellitus, family income, caretaker marital and employment status, protective services involvement, and paternal involvement. * On final step, with all variables entered. y Absolute ounces of alcohol per day, averaged across pregnancy. z Pattern considered positive if R 5 drinks were consumed per occasion at least once every 2 weeks during pregnancy.
clinically significant levels of delinquent behavior (17% vs 7%; c2 (1) = 7.75; P ! .01).
Comment Prenatal alcohol exposure was significantly related to both decreased IQ score and increased behavior problems in this large sample of black first grade students. Children who were exposed to binge drinking prenatally, regardless of the amount of overall pregnancy exposure, had significantly lower verbal IQ scores and significantly higher levels of teacher-reported delinquent behavior compared with the remaining children, even after control for other prenatal exposures and postnatal environmental factors (including current alcohol exposure, maternal IQ, quality of home environment, socio-
Stepwise regression results for delinquent behavior
Exposure Amount of alcohol exposurey Quality of home environment Child violence exposure Prenatal exposure Cigarettes Cocaine Amount of alcohol Pattern of alcohol exposurez Quality of home environment Child violence exposure Prenatal exposure Cigarettes Cocaine Pattern of alcohol
R
R2 change
.15
t*
P value
.023
3.96
!.001
.20
.016
2.84
.005
.22
.008 .71 .66 1.68
.480 .510 .100
.15
.024
3.38
.001
.20
.016
2.81
.005
.23
.013 .70 .80 2.26
.485 .427 .024
Significant covariates included child age, gender, lead level, violence exposure, maternal verbal IQ, psychopathology, depression, age, socioeconomic status, custody changes, current alcohol exposure, number of children in home, and quality of home environment. Additional covariates (nonsignificant relations with both prenatal alcohol and outcomes) that were considered included child Apgar scores, number of hospitalizations, medical diagnoses, and preschool attendance, number of prenatal visits, pregnancy hypertension, pregnancy diabetes mellitus, family income, caretaker marital and employment status, protective services involvement, and paternal involvement. * On final step, with all variables entered. y Absolute ounces of alcohol per day, averaged across pregnancy. z Pattern considered positive if R 5 drinks were consumed per occasion at least once every 2 weeks during pregnancy.
economic status, and violence exposure). Thus, the pattern of prenatal alcohol exposure was an even more important determinant of outcomes than volume in this large-scale prospective study. Results of the current study support the findings of other researchers who suggest that exposure to binge drinking has more deleterious consequences than the overall amount of exposure to alcohol during pregnancy.10,14 Binge drinking, which produces higher blood alcohol content, produces a higher threshold of exposure and exposes the fetus to alcohol for a longer period of time, both of which are likely to have a more profound effect on developing structures.11 Animal studies appear to support this contention. Rats that are exposed to bingelike prenatal alcohol exposure have more severe brain injury than rats that are exposed to the same amount of alcohol over a longer period.20 Similar studies have reported brain damage after a single instance of binge exposure.21 Thus, findings of the current investigation
1042 demonstrate that simply looking at the overall amount of exposure may obscure important prenatal alcohol exposure effects. This may be one reason why several researchers have failed to find an effect of prenatal alcohol exposure on child cognitive and behavioral outcomes.7-9 An interesting finding of the current study is the lack of an association between binge drinking exposure and performance IQ. Like other researchers, we demonstrated a link between prenatal alcohol exposure (in our case binge drinking exposure) and verbal IQ.4,10 However, exposure and performance IQ were not related. This finding may be due to the characteristics of our sample, which include significant variance in performance IQ scores attributable to confounding variables. Still, a few other studies have reported similar findings22 and posit how this potential difference may indicate specific, rather than global, effects of prenatal alcohol exposure on cognition.23 The current study has many strengths, which include a large sample size, prospectively collected prenatal alcohol exposure that includes the measurement of binge drinking, the assessment of the children 7 years after birth, and the inclusion of many confounders. However, the study could be improved by including additional measures of cognition, as the effects of prenatal alcohol exposure may be quite specific. In addition, the current study is limited in generalizability as it excluded women with no prenatal care and included only black families who lived in the Detroit area. Despite these limitations, these results provide further evidence, from a study with significant statistical power and sound methodology, that pattern of prenatal alcohol exposure plays a significant role in child outcomes. Further investigation is warranted to replicate these findings and to include more specific outcome measures. Finally, it is important to recognize the implications for prenatal care. Pregnant women who drink heavily are routinely advised of the potential consequences and encouraged strongly to cease or at least to cut back intake. However, if cutting back involves drinking less often, but still consuming large amounts when intake occurs, offspring may not experience improved outcomes. Understanding the consequences of prenatal exposure to binge drinking is especially important because surveys indicate that women of childbearing age who consume alcohol are more likely to binge than drink in a chronic heavy pattern.24 Clinicians should continue to advise against drinking any alcohol during pregnancy and should emphasize that the amount of alcohol that is consumed per occasion may be a more critical factor than the overall number of drinks that are consumed per week. Such understanding and emphasis could go a long way toward decreasing the severity of associated outcomes and the number of children who are born with fetal alcohol syndrome and fetal alcohol spectrum disorder.
Bailey et al
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1043 mental manifestations. New York: Guilford Press; 1995.;265: p. 5-32. 24. Wechsler H, Lee JE, Kuo M, Seibring M, Nelson TF, Lee H. Trend in college binge drinking during a period of increased prevention efforts: findings from 4 Harvard School of Public Health College alcohol surveys. J Am Coll Health 2002; 50:203-17.