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Early Fetal Binge Alcohol Exposure Predicts High Behavioral Symptom Scores in 5.5-Year-Old Children

Authors

  • Astrid Alvik,

    Corresponding author
    1. Division of Mental Health and Addiction, Institute of Clinical Medicine University of Oslo, Oslo, Norway
    2. Child and Adolescent Mental Health Research Unit, Oslo University Hospital, Oslo, Norway
    • Reprint requests: Astrid Alvik, MD, PhD, Child and Adolescent Mental Health Research Unit, Oslo University Hospital, PO Box 4959 Nydalen, N-0424 Oslo, Norway; Tel.: +47 23 49 21 00, Fax: +47 23 49 23 02; E-mail: astrid.alvik@medisin.uio.no

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  • Odd O. Aalen,

    1. Department of Biostatistics , Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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  • Rolf Lindemann

    1. Department of Paediatrics , Oslo University Hospital, Oslo, Norway
    2. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Abstract

Background

Fetal binge alcohol exposure has been associated with neurobehavioral and cognitive symptoms. This study explored whether binge drinking mainly before recognition of pregnancy predicted high symptom scores on the Strengths and Difficulties Questionnaire (SDQ) in 5.5-year-old children.

Methods

In a population-based, longitudinal study representative of pregnant women in Oslo, Norway, questionnaires were answered at 17 and 30 weeks of pregnancy, 6 months after term, and at child age 5.5 years (n = 1,116, constituting 66% of the original cohort). Logistic regression analyses identified factors predicting high SDQ scores, and multiple regression analyses identified direct effects on the SDQ Total.

Results

Binge exposure (≥5 standard units per occasion [SUpo]) during pregnancy week 0 to 6, that is, 0 to 4 weeks after conception, predicted scores in the Abnormal and Borderline range on the SDQ in 5.5-year-olds, after adjusting for other confounding variables. Very early binge exposure less often than once a week predicted high symptom scores on the SDQ Total (= 0.05) and Hyperactivity/Inattention (significant), while exposure at least once a week demonstrated a 3- to 5-fold significant increase in high symptom scores on Total, Emotional, and Conduct problems. Reporting ≥8 SUpo had stronger predictive power than reporting 5 to 7 SUpo. The results were not explained by participants reporting major lifetime depression. Other predictive factors, although weaker, were maternal symptoms of depression and anxiety during the child's infancy. High education (mother and father), high income (maternal partner), higher child birth weight, and child female sex reduced the likelihood of high SDQ symptom scores. Path analysis demonstrated early binge exposure to have a direct effect on the SDQ Total score.

Conclusions

Binge drinking up to 4 weeks after conception had a strong and direct predictive effect on SDQ symptom scores in 5.5-year-olds. These results strongly support the advice to avoid binge drinking when planning pregnancy.

It has been well documented that children exposed to higher levels of prenatal alcohol consumption may display physical deformities in addition to neurobehavioral and cognitive problems. This may include mental retardation and a broad specter of psychiatric and social problems (Fryer et al., 2007; Jones et al., 1973; Kelly et al., 2000; Mattson and Riley, 1998; O'Connor and Kasari, 2000). Light-to-moderate drinking during pregnancy may primarily affect subtle neurobehavioral outcomes (Barr et al., 2006; Henderson et al., 2007; Kelly et al., 2000; Mattson and Riley, 1998; O'Connor and Kasari, 2000; Sood et al., 2001; Streissguth et al., 1990). However, moderate drinking and binge drinking (≥3 drinks at least once a month) have been found to be a risk factor for both lower birth weight and neonatal asphyxia (Meyer-Leu et al., 2011). Reporting any binge drinking (≥5 drinks) during the first trimester has been associated with increased risk of oral clefts (DeRoo et al., 2008), and consumption of only 2 to 3.5 drinks per week during the first trimester has been associated with an increased chance of fetal death (Andersen et al., 2012).

The animal studies, with their possibility of using an experimental design, have contributed considerably within this field of research. These studies have revealed that a drinking pattern causing a higher blood alcohol concentration (BAC) may be particularly devastating to the offspring (Bonthius and West, 1990; Ikonomidou et al., 2000). Even a single dose of binge-like alcohol exposure has been shown to result in neural cell death and microencephaly (Bonthius and West, 1990; Goodlett and Eilers, 1997; Ikonomidou et al., 2000). Also, exposure equivalent to the time before pregnancy recognition has resulted in neural cell death (Valles et al., 1996). In addition, exposure very early during pregnancy has been demonstrated to be as serious to offspring behavior as late gestation or continuous exposure (Clarren et al., 1992; Schneider et al., 2001).

Observational studies in humans generally demonstrate results corresponding to those found in experimental animal studies. A drinking pattern causing a higher BAC during pregnancy has been shown to be associated with increased level of behavioral/psychiatric or cognitive problems, compared with more evenly distributed alcohol consumption (Bailey et al., 2004; Jacobson et al., 1998; Streissguth et al., 1990). Prenatal binge exposure (≥5 drinks) on at least 1 occasion has been associated with more learning problems at 7 years of age (Streissguth et al., 1990) and with more psychiatric disorders among young adults (Barr et al., 2006). Further, 1 study showed that 1 binge episode (≥4 drinks) after the first trimester was associated with an increased likelihood of child behavioral problems, as measured by the parent-completed Strengths and Difficulties Questionnaire (SDQ) (Sayal et al., 2009). This study included the SDQ Total, Conduct problems, and Hyperactivity/Inattention scores. Early pregnancy binge exposure has been shown to be associated with a greater degree of disinhibited behavior (Nulman et al., 2004). Also, in an earlier report from the present sample, 6-month-old infants exposed to binge drinking (≥5 drinks) at least once a week up to 4 weeks after conception, were shown to have a 3- to 5-fold increased likelihood of difficult temperament and sleeping problems (Alvik et al., 2011).

In the present, population-based study, at least 1 binge episode was reported by 60% during the last 6 months prior to pregnancy and by 25% during pregnancy weeks 0 to 6 (Alvik et al., 2006b). Little alcohol consumption was reported after pregnancy recognition. As more than 99% attend free prenatal care in Norway, this is a suitable country to study possible effects of early binge drinking in a representative sample.

The SDQ is a 25-item measure of 4- to 16-year-olds covering 4 psychopathology scales (Emotional symptoms, Conduct problems, Hyperactivity/Inattention, and Peer problems). They can be added up to a Total problem score. The SDQ also includes a Prosocial scale (Goodman, 2001). The SDQ has been validated in several studies showing good psychometric properties (Goodman, 2001; Goodman and Scott, 1999; Rønning et al., 2004) and is now widely used internationally. It has been translated into all Nordic languages (Obel et al., 2004).

Our hypothesis was that, in adjusted analyses, very early binge fetal exposure would increase the likelihood of scoring in the Abnormal and Borderline or Abnormal range on the SDQ Total, Emotional, Conduct, and Hyperactivity/Inattention problem scales, but not on the Peer problem and Prosocial scales, in 5.5-year-old children.

Materials and Methods

The data used in this study are part of a longitudinal, questionnaire study. In Norway, all pregnant women attend a free ultrasound screening at 17 to 18 weeks of pregnancy. A representative sample of pregnant women in Oslo attends this at Oslo University Hospital, Ullevaal. Women attending ultrasound screening between June 2000 and May 2001 were invited to join the study, accepted by 92% (n = 1,873). They had received an information letter about the study, underlining the full confidentiality, also toward their own doctor and midwife. Non-Scandinavian speaking and/or immigrants from non-Western countries were not invited. For further details, see Alvik and colleagues (2006a).

The first questionnaire (Q1: 17 weeks of pregnancy) was filled out at the antenatal clinic where the women could sit privately. The questionnaire was completed by 1,749 women (i.e., 93% of those who joined and 86% of those invited to join the study). After completion, it was placed in a sealed envelope in a locked box. The only identification on the questionnaires was a unique code. The second and third questionnaires (Q2: 30 weeks of pregnancy; Q3: 6 months after term) were sent by mail to those returning the previous questionnaire, except 19 participants (8 miscarriages, 6 stillbirths, and 5 unconfirmed live infants). They were returned by 1,424 (Q2) and 1,303 (Q3) participants, 82% and 92%, respectively. The fourth questionnaire (Q4: child age 5.5 years) was sent by mail to those who returned Q1, except 63 women who had a miscarriage or stillbirth, or discontinued participation. Q4 was sent to 1,686 women and returned by 1,116 (constituting 66% of the original cohort). At Q4, the data set included 1,138 children (23 sets of twins with 45 live children).

The 4 questionnaires included the following items: Q1: Binge drinking (both 5 to 7 and ≥8 standard units [SU] per occasion [po]) during pregnancy weeks 0 to 6, with frequency options: several times/week; once a week; 1 to 3 times/mo; more seldom than 1 to 3 times/mo; never). If there was a nonresponse on any one of the questions/columns combined with “never” on the other, binge drinking was treated as missing. Also included in Q1: maternal age, smoking in the second trimester, a history of major lifetime depression; Q2: stressful work during pregnancy; Q3: SU per week during the third trimester (usual frequency times usual amount), and a 13-item version of Hopkins Symptom Checklist (H-SCL) divided into subscales of H-SCL depression (8 items) and H-SCL anxiety (5 items) (Derogatis et al., 1974). Missing items were replaced by the item sample mean. Cases exceeding 2 missing items on the 5-item and 3 on the 8-item versions were considered missing. Also included in Q3: infant medical problems; Q4: SDQ, a behavioral questionnaire for parent completion including 25 items covering 5 scales: Emotional symptoms, Conduct problems, Hyperactivity/Inattention, Peer problems, and Prosocial behavior (Goodman, 2001); also included in Q4: maternal civil status, education (mother and father), income (mother and partner), child sex and having siblings, and being a twin. From the Medical Birth Registry of Norway (MBRN), data concerning birth complications, infant birth weight, and 5-minute Apgar score were collected.

Weeks of pregnancy was defined from the first day of the last menstruation.

All women provided written informed consent and permitted collection of data from the MBRN. The Regional Committee for Medical Research Ethics and the Norwegian Data Inspectorate approved the study.

Statistical Methods

SPSS for Windows Version 16.0. (SPSS Inc., Chicago, IL) was used for all statistical analyses. A high symptom SDQ score was defined as a score in the Abnormal and Borderline, or in the Abnormal, range; that is, scoring at or above the 80th percentile, or ≥90th versus <80th percentile in the sample (for Prosocial behavior, ≤20th and 10th percentile). Pearson's chi-square was used for comparing SDQ scores in the binge-exposed and nonexposed groups and to explore potential associations between early binge drinking and several covariates. Binary logistic regression analyses were used to identify variables predicting high symptom scores on the SDQ problem scales and low score on the Prosocial behavior scale. The independent variables concerning the mother were as follows: binge drinking during pregnancy weeks 0 to 6 (never; <once a week; ≥once a week) and age (continuous), and the following dichotomized: civil status (married/cohabitant vs. other), H-SCL anxiety and depression (<1.75 symptomatic anxiety 10.2%; depression 13.5%), and dichotomized into yes/no: any alcohol use during the third trimester, major lifetime depression, studied at university or college, higher income, smoking, and stressful work during pregnancy. The independent variables concerning the child included birth weight (continuous; kg with decimals) and sex, and the following were dichotomized into yes/no: 5-minute Apgar score (<7), having siblings, and infant medical problems. Both univariable (unadjusted) and multivariable (adjusted) analyses including other possible predictive variables were performed. All factors with a significance level below 0.25 in univariable analysis were brought into the model. The least significant factors were excluded one by one until the remaining factors were significant at the = 0.05 level. The Hosmer and Lemeshow goodness of fit test was used to evaluate the final models.

As the proportion of twins was small (22 of 1,116 mothers reported for 2 children), the potential lack of independence in the data is expected to be negligible and has not been corrected for. None of the twin mothers reported frequent binge drinking, and binge drinking less often was not reported differently from the single-birth mothers.

A path analysis was performed using multiple linear regression with birth weight, maternal anxiety, and depression 6 months after term (both continuous) successively as dependent variables, followed by a hierarchical linear regression with the SDQ Total score (continuous) as the dependent variable. In these analyses, early binge was dichotomized into yes/no, while the other variables were as described above.

Results

The maternal characteristics are described in Table 1 and in the 'Materials and Methods' section. The alcohol use and binge drinking in this data set, and predictors of these variables, have previously been reported (Alvik et al., 2006b). Reduction in alcohol use mainly occurred at pregnancy recognition, which primarily occurred between weeks 5 to 6 (cumulative: from 35 to 90%). The questions concerning binge drinking during pregnancy had a high item nonresponse (11%). Thus, information about binge exposure during pregnancy weeks 0 to 6 was available for 1,003 of the 1,138 children. In the present sample, 222 children (22%) were exposed to early binge less often than once a week, 162 of them less often than once a month. Thirty-two children (3.2%) were exposed at least once a week. Early binge drinking was not significantly associated with maternal history of major lifetime depression, H-SCL anxiety or depression, birth complications, 5-minute Apgar score, infant medical problems, or being a twin (Pearson's chi-square = 0.99; 0.39; 0.94; 0.23; 0.96; 0.87; and 0.66, respectively). Higher level of binge (≥8 SUpo) was reported by 53% of those reporting both infrequent and frequent early binge. Binge drinking after week 7 was reported by 54 participants, 28 in the second, and 27 in the third trimesters. Except 2 reporting frequent binge, they all reported infrequent binge and 75% reported binge less often than once a month. At least 8 SUpo was reported by15 and 16 participants in the second and third trimesters. Any use of alcohol was reported by 34% during the third trimester, all nonabstinent women reporting <2 SU/wk except 4 who reported 2 to 4 SU/wk. No participant reported use of heroin or cocaine during pregnancy, but 3 women reported use of hashish. One of these also used ecstasy and amphetamine. She reported no alcohol use, as did 1 of the other women, while the third reported binge 5 to 7 SUpo both before and after pregnancy week 7. Fifty-one percent of the children were boys.

Table 1. Maternal Characteristics
 Mean (SD) or %
  1. a

    Reported at pregnancy weeks 17 to 18, selecting the participants who have answered Questionnaire 4 (Q4).

  2. Higher education: had qualified from, or studied at, the university or college; higher income: more than NOK 400,000 (Norwegian crowns, equaling approximately 44,400 USD or 30,800 € at the time of Q1).

Maternal agea30.9 (4.2)
Higher education79%
Higher income28%
Married or cohabitant89%
Child having siblings89%

Children exposed to very early pregnancy binge drinking had an increased likelihood of attaining a high symptom score on the SDQ Total, Emotional problems, Conduct problems, and Hyperactivity/Inattention (Table 2).

Table 2. Percentage of Children in Each Scoring Category of Strengths and Difficulties Questionnaire to Have Been Exposed to Early Pregnancy Binge Drinking
 Total sampleBinge pregnancy weeks 0 to 6
% (n) n No % (n)<Once a week % (n)≥Once a week % (n)
  1. n, Number.

  2. *< 0.05, **< 0.01, ***< 0.001.

  3. Using Pearson's chi-square; percentage in columns.

Total(1,129)996**   
Normal73 (829) 76 (569)69 (151)45 (14)
Borderline17 (186) 15 (114)18 (40)36 (11)
Abnormal10 (114) 8 (62)13 (29)19 (6)
Emotional symptoms(1,136)1,002*   
Normal72 (812) 74 (554)65 (144)52 (16)
Borderline14 (151) 13 (96)15 (34)23 (7)
Abnormal15 (173) 13 (100)20 (43)26 (8)
Conduct problems(1,134)1,000*   
Normal74 (838) 75 (558)75 (165)53 (17)
Borderline15 (175) 15 (112)16 (36)19 (6)
Abnormal11 (121) 10 (78)9 (19)28 (9)
Hyperactivity/Inattention(1,135)1,001***   
Normal67 (756) 69 (517)58 (129)56 (18)
Borderline21 (143) 21 (155)28 (61)13 (4)
Abnormal12 (136) 10 (76)14 (31)31 (10)

In univariable analyses, high symptom SDQ scores were predicted by exposure to smoking, early binge drinking, maternal stressful work during pregnancy, maternal civil status (not married or cohabitant), mental health problems, and infant medical problems (Table 3). The likelihood of high scores was reduced with increasing maternal age, parental education and income, infant increasing birth weight, and female sex. A low Apgar score approached significance to predict the Total score (Abnormal; = 0.051, OR 3.3), and stressful work during pregnancy was close to predicting Hyperactivity/Inattention (Abnormal and Borderline; = 0.052, OR 1.3). Any alcohol use during the third trimester had no predictive power. There was a trend that being a twin (n = 45) increased the chance of low scores on the SDQ Total and Emotional problems in unadjusted analyses (= 0.073 and 0.10, OR 2.1 for both). However, after including birth weight in the analyses, being a twin had no predictive power. Very early binge exposure had no predictive power concerning Abnormal and Borderline or Abnormal scores on the SDQ Peer problems and Prosocial scales.

Table 3. Factors Significantly Associated with a Score in the Abnormal and Borderline Versus the Normal Range in Strengths and Difficulties Questionnaire at 5.5 Years of Age, and in the Abnormal Versus the Normal Range. Univariable (Unadjusted) Logistic Regression; Odds Ratios
Reported at Strengths and Difficulties Questionnaire
Abnormal and borderline versus normalAbnormal versus normal
TotalEmotionalConductHyper/InatTotalEmotionalConductHyper/Inat
  1. Hyper/Inat: hyperactivity/inattention, Medical prb c: medical problems child, Q1: pregnancy week 17, Q2: pregnancy week 30, R: Medical Birth Registry of Norway, Q3: 6 months after term, H-SCL: Hopkins Symptom Checklist, Q4: child 5.5 years, pw: pregnancy week, c: child, m: mother, f: father, m.part: mother's partner.

  2. *< 0.05, **< 0.01 and ***< 0.001.

  3. Normal range <80th percentile, Borderline ≤80th and < 90th percentile, Abnormal ≥90th percentile. Variables not reaching significance: R: birth complications, 5-minute Apgar score (see text); Q3: any alcohol use during pregnancy months 6 to 9; Q4: child having siblings.

Q1Maternal age0.95**0.95**0.97*0.95**0.94*0.93***0.95*0.94**
Smoking1.5*  1.9**1.8*  2.3**
Binge pw 0–6: *** ** * ** ** ** ** **
No(Ref)(Ref)(Ref)(Ref)(Ref)(Ref)(Ref)(Ref)
<Once a week1.5*1.5* 1.6**1.8*1.7* 1.6*
≥Once a week3.9***2.7**2.6** 3.9**2.8*3.8**3.8**
Major lifetime depression1.9**2.4*** 1.6*2.1*2.8*** 2.0*
Q2Stressful work       1.6*
RBirth weight c0.68**0.79*0.70**0.74**0.50***0.73*0.56***0.60**
Q3H-SCL anxiety2.0** 2.2** 2.4**1.8*2.3** 
H-SCL depression2.3***2.1**1.9**1.5*2.7**2.7***2.4**1.8*
Medical prb c      2.0* 
Q4Civil status1.5*  1.5*1.9*  1.8*
Education m0.52***  0.54***0.47**  0.42***
Education f0.54***0.67**0.72*0.51***0.49**0.63* 0.47***
Income m.part0.70*0.63**0.71*0.72* 0.67*0.61* 
Female sex c   0.71*    

In multivariable (adjusted) analyses, the variable most consistently predicting a high SDQ symptom score was very early binge drinking, followed by maternal depression during the child's infancy (Table 4). Exposure to infrequent early binge drinking (less often than once a week) predicted Abnormal and Borderline scores on the SDQ Total (= 0.050) and Hyperactivity/Inattention (= 0.013). Exposure to frequent early binge drinking (≥once a week) predicted an Abnormal and Borderline score on Total, Emotional, and Conduct problems (= 0.001, 0.012, and 0.045) and predicted an Abnormal score on Total, Conduct problems, and Hyperactivity/Inattention (= 0.005, 0.007, and 0.021). SDQ problem scores were also predicted by maternal symptoms of depression and anxiety during the child's infancy and by maternal history of major lifetime depression. The likelihood was reduced by parental high education (mainly paternal, but also maternal) and high income (maternal partner), infant increasing birth weight, and female sex (Table 4). Infant female sex predicted reduced likelihood for problem scores on Hyperactivity/Inattention only, but approached an increased likelihood of an Abnormal and Borderline score on the Emotional scale (= 0.064, OR 1.4, 95% CI 0.98 to 1.87). Exposure to smoking and stressful work during pregnancy had no predictive power in the adjusted analyses. This was also the case for any alcohol use during the third trimester, birth complications, 5-minute Apgar score, infant medical problems, maternal civil status and high income, and the child having siblings.

Table 4. Factors Predictive of a Score in the Abnormal and Borderline Versus the Normal Range in Strengths and Difficulties Questionnaire at 5.5 Years of Age, and a Score in the Abnormal Versus Normal Range. Multivariable (Adjusted) Logistic Regression
Reported at Strengths and Difficulties Questionnaire
Abnormal and borderline versus normal OR (95% CI)Abnormal versus normal OR (95% CI)
TotalEmotioConductHyper/InatTotalEmotioConductHyper/Inat
  1. Emotio: emotional, Q1: pregnancy week 17, R: Medical Birth Registry of Norway, Q3: 6 months after term, H-SCL: Hopkins Symptom Checklist, Q4: child 5.5 years, Binge 0 to 6: binge drinking during pregnancy weeks 0 to 6, Maj lifet depression: major lifetime depression, HL: Hosmer and Lemeshow goodness of fit test, c: child, m. partner: mother's partner.

  2. *< 0.05, **< 0.01, ***< 0.001, and = 0.05.

  3. The following variables were not included in the table as they had no p-value <0.05: Q1: smoke at T1; Q2: daily stressful work during pregnancy; R: birth complications, 5-minute Apgar score; Q3: Any alcohol use during pregnancy months 6 to 9, infant medical problems; Q4: maternal civil status, maternal high income, child having siblings.

Q1Maternal age     0.95* (0.90 to 0.99)  
Binge 0–6: ** * * * *   * *
No(Ref)(Ref)(Ref)(Ref)(Ref)(Ref)(Ref)(Ref)
< Once a week1.5 (1.0 to 2.1)  1.5* (1.1 to 2.2)    
≥Once a week4.1** (1.7 to 9.8)3.2* (1.3 to 8.0)3.0* (1.3 to 7.2) 4.9** (1.6 to 14.8) 4.1** (1.5 to 11.4)3.1* (1.2 to 8.1)
Maj lifet depression     2.6** (1.5 to 4.4)  
RBirth weight c0.66** (0.51 to 0.87) 0.75* (0.57 to 0.99)0.69** (0.54 to 0.88)0.48*** (0.33 to 0.71) 0.56** (0.38 to 0.81)0.55** (0.39 to 0.79)
Q3H–SCL anxiety  2.3** (1.3 to 4.0)     
H–SCL depression2.4** (1.4 to 4.0)2.5** (1.5 to 4.1)  2.6** (1.3 to 5.4)2.5** (1.4 to 4.4)2.4* (1.2 to 4.8) 
Q4Education mother   0.64* (0.44 to 0.95)    
Education father0.54** (0.38 to 0.76)0.64* (0.44 to 0.92) 0.64* (0.46 to 0.90)0.43** (0.26 to 0.72)0.61* (0.40 to 0.92) 0.43*** (0.27 to 0.68)
Income m. partner 0.61** (0.44 to 0.86)0.59** (0.42 to 0.83)   0.52** (0.32 to 0.85) 
Female sex c   0.68* (0.51 to 0.92)   0.64* (0.41 to 1.0)
HL0.120.510.810.500.140.860.720.73

Additional analyses were performed exploring predictors of high Abnormal and Borderline scores, excluding 1 group per analysis. First, the 134 participants reporting early binge ≥8 SUpo at least once were excluded. In adjusted analyses, a high score was predicted by frequent very early binge 5 to 7 SUpo (Emotional: = 0.016, OR 14.5, 95% CI 1.6 to 127.8). Also, very early exposure of 5 to 7 SUpo approached significance on Total scale (= 0.058), with frequent exposure being significant (= 0.017, OR 7.8, 95% CI 1.5 to 42.3). Thereafter, the 54 participants reporting binge drinking both before and after pregnancy week 7 were excluded. In adjusted analyses, infrequent very early binge exposure predicted a high Hyperactivity/Inattention score (= 0.011, OR 1.6, 95% CI 1.1 to 2.3), while frequent binge exposure predicted high Total, Emotional, and Conduct problems scores (p, OR, 95% CI: 0.001, 4.4, 1.8 to 10.9; 0.008, 3.6, 1.4 to 9.2; and 0.004, 3.6, 1.5 to 8.7, respectively). Finally, the 105 participants reporting major lifetime depression were excluded. Infrequent early binge predicted a high Hyperactivity/Inattention score (adjusted = 0.10, OR 1.6, 95% CI 1.1 to 2.3), and frequent early binge predicted high Total, Emotional, and Conduct problems scores (adjusted p, OR, 95% CI: 0.003, 4.1, 1.6 to 10.4; 0.010, 3.8, 1.4 to 10.3; and 0.005, 3.4, 1.5 to 7.9, respectively).

Path analysis performed with the SDQ Total as the final dependent variable demonstrated that early binge had a direct effect on the SDQ Total score and not an indirect effect via birth weight or maternal anxiety or depressive symptoms (Fig. 1). Smoking, however, only had an indirect effect on the SDQ Total score.

Figure 1.

Path analysis; Variables with effect on Strengths and Difficulties Questionnaire (SDQ) Total. Hierarchical multiple regression. Q1: pregnancy week 17; MBRN: Medical Birth Registry of Norway; Q3: 6 months after term; Q4: child 5.5 years old; Maj.lifet.dep: major lifetime depression. *p < 0.05, **p < 0.01, ***p < 0.001.

Discussion

The main finding in this population-based study was that exposure to binge drinking in the time span before most women knew they were pregnant predicted high SDQ symptom scores in the Abnormal and Borderline or Abnormal range in 5.5-year-old children, confirming our hypothesis. In adjusted analyses, infrequent binge exposure within 4 weeks after conception predicted high symptom scores on SDQ Total and Hyperactivity/Inattention, while binge exposure at least once a week predicted Total, Emotional, and Conduct problem scores. The results were not driven by the participants reporting binge drinking later during the pregnancy or those reporting major lifetime depression. Further, reporting a higher-level early binge drinking had stronger predictive power than reporting 5 to 7 SUpo, indicating a dose–response effect, but report of any binge drinking 5 to 7 SUpo still predicted high symptom scores. Very early binge exposure was the strongest predictor of high SDQ scores, and had a direct effect on the symptom scores of the SDQ Total. In this population with little poverty, the majority reported binge drinking during the last 6 months prior to pregnancy. The change in alcohol use occurred at recognition of pregnancy, that is, between 2 to 4 weeks after conception, for the vast majority, with little alcohol consumption thereafter. There were no associations between very early binge drinking and maternal mental health, birth complications, or infant health covariates. The report of illegal drugs was negligible.

In line with our hypothesis, there were no associations between very early binge exposure and adverse effects on the Peer problems and Prosocial scales.

Several studies have reported fetal alcohol binge exposure to be associated with adverse effects for the offspring. Such exposure has been found to be associated with functional deficits in infants (Jacobson et al., 1998) and with learning problems, mental retardation, and delinquent behavior in 7-year-old children (Bailey et al., 2004; Streissguth et al., 1990). Also, it has been associated with antisocial behavior, school problems, and self-perceived learning difficulties in 14-year-old children (Olson et al., 1997). A recently published study reported decreased fetal information processing, reflected by poorer habituation, after moderate binge exposure (5 to 10 SU/wk on 2 to 3 drinking days throughout pregnancy) (Hepper et al., 2012). Although few studies have reported on potential consequences following exposure primarily before pregnancy recognition, 1 study showed that very early binge exposure was associated with behavioral differences, with the exposed group displaying greater disinhibited behavior than controls (Nulman et al., 2004). This study primarily investigated social drinkers concerned about having had 1 or more binge episodes prior to recognition of pregnancy. Thus, the finding that very early binge exposure predicts high problem scores is in line with a previous study. In a previous study using data from the same participants, we demonstrated more infant sleep and temperament problems in these early exposed children (Alvik et al., 2011). The results of the current study, investigating children at the age of 5.5 years, thus also expand the age where adverse effects of very early binge drinking are demonstrated. Further, the results of this population-based study mainly including participants with high education and few risk factors also expand and replicate the findings from other studies, examining disadvantaged societies (Jacobson et al., 1998; Olson et al., 1997).

A recently published Danish study of 5-year-olds found higher-level early fetal binge exposure (≥9 SUpo) to be associated with low attention score (Underbjerg et al., 2012). However, no adverse effects were associated with exposure 5 to 8 SUpo, contradicting the results in the present study (Kesmodel et al., 2012; Underbjerg et al., 2012). A difference in the data collection method concerning alcohol use could potentially explain this difference. The present study used self-administered questionnaires (SAQs), while the Danish study used telephone interviews to reduce the item nonresponse (Olsen et al., 2001). The rate of reported alcohol use has been found to be higher using SAQ compared with face-to-face interviews (Rogers et al., 1998), which again has been higher than using telephone interview (Aquilino, 1992). Particularly for sensitive questions, methodological differences such as these may have a substantial effect, the importance increasing with the sensitivity (Bjarnason and Adalbjarnardottir, 2000; Ong and Weiss, 2000; Singer et al., 1995). Further, participants may be liable to give a more socially acceptable answer, using methods with less perceived anonymity (Bjarnason et al. 2000). In the present study, the direct questions about alcohol use during pregnancy were the most sensitive questions (Alvik, 2007; Alvik et al., 2005b). The item nonresponse was indeed high in our study, but only for the sensitive questions (11 to 15% for alcohol use during pregnancy) (Alvik et al., 2005b). As both the percentage reporting alcohol use and the item nonresponse may be lower using telephone interviews compared with SAQ, a far from negligible proportion of the nonexposure group may have underreported actual alcohol exposure using telephone interviews. This will reduce the difference between the groups. It is preferable that participants reluctant to admit unwanted behavior may choose item nonresponse and are thus left out of the analyses, as in our study using SAQ.

Infrequent binge exposure after the first trimester has been associated with higher problem scores on the SDQ (Sayal et al., 2009). The present study replicated these results, demonstrating that SDQ problem scores were associated with binge fetal exposure. However, the results of the present study expand the time of possible harm into very early pregnancy. In the Sayal and colleagues (2009) study, there were indications that girls had an increased vulnerability to the binge exposure, especially concerning Hyperactivity/Inattention. This finding was not replicated in the present study. On the contrary, girls had a reduced likelihood of achieving high problem scores on Hyperactivity/Inattention. This is in line with knowledge that fewer girls than boys are diagnosed with attention-deficit/hyperactivity disorder (Mahone and Wodka, 2008).

In animal studies, 1 binge exposure has been shown to result in neural cell loss (Bonthius and West, 1990; Goodlett and Eilers, 1997; Ikonomidou et al., 2000), which has also been demonstrated during very early pregnancy (Cartwright and Smith, 1995). Thus, the results of the present study are supported by findings from animal studies.

Although there are difficulties extrapolating the results to humans, the animal studies have a major advantage in that differences between groups can be ameliorated. In humans, innumerable pre- and postnatal factors may contribute to the neurodevelopmental outcomes. The women who consume some alcohol generally have higher education and income, fewer mental health problems, are more social, and consume more alcohol during pregnancy, compared with abstainers (Alvik et al., 2006b; Dejin-Karlsson et al., 1997). This low or mainstream consumer group, or their children, could be expected to attain more optimal outcomes. Thus, a randomized clinical trial would be the method of choice to compare an abstainer group with a group consuming light or moderate amounts. However, studying alcohol exposure during pregnancy in humans, using this method, would be highly unethical. The research method used to control for other covariates may be insufficient. As the low- to moderately exposed group generally may have more beneficial characteristics, the demonstrated effect of alcohol may be smaller than the real effect of alcohol. Thus, theoretically, at the level of social drinking, beneficial effects in the exposed group could emerge based on insufficient covariate adjustment.

In nonexperimental studies, one can never exclude the possibility that differences between groups in reality are caused by unmeasured variables. Thus, as in all observational studies, there is the possibility that potential confounding variables have not been measured in the present study, although a variety of covariates have been adjusted for.

There are several strengths to the current study. First, it is a population-based study with multiple waves of data collection, with a relatively high response rate. The participants were generally well educated, had few risk factors, and reported little alcohol use after pregnancy recognition (Alvik et al., 2006b). Further, we made an effort to reduce underreporting by maximizing the perceived anonymity and by using SAQs and carefully designing the questions: The binge drinking questions offered several high-frequency alternatives listed before low frequencies or no binge alternatives. Thus, the more extreme values could also be excluded. To estimate the problem of underreporting, we have previously compared confidential and anonymous questionnaires (Alvik et al., 2005b) and concurrent and retrospective reports of alcohol use (Alvik et al., 2005a). With regard to alcohol use during pregnancy, retrospective reporting was found to reduce the underreporting, particularly with regard to average use. Thus, the inclusion of measures of average use reported 6 months after pregnancy, and early binge reported in the second trimester, is considered a strength of the study. Norway had a low “alcohol per capita” in 2001 (5.5 l; mean in Europe/United States was 10.1/8.5 l) (World Resource Institute, 2011). The high percentage of participants reporting very early pregnancy binge drinking further indicates a modest degree of underreporting. Also, it should be mentioned that during the last decade prior to the study, there was no official warning concerning alcohol consumption during pregnancy in Norway, and information about possible fetal alcohol damage was very limited. The use of SDQ could also be considered a strength, as it has been well validated and has been widely used both in research and clinically (Goodman, 2001; Goodman and Scott, 1999; Obel et al., 2004; Rønning et al., 2004).

The study also has some limitations. Underreporting of binge drinking during pregnancy might be expected. This is, however, less likely to occur before, compared with after, pregnancy recognition (Alvik et al., 2005b). As expected for sensitive questions in epidemiological samples, there was a high item nonresponse on the items concerning binge drinking during pregnancy (Alvik et al., 2005b). However, on sensitive items in questionnaire studies, this could indicate a higher validity of the given answers, compared with an interview setting where a socially acceptable answer might be preferred. Further, the participants provided all information themselves, thus potentially their mood could have influenced their report. However, the parental SDQ report has been found to have satisfactory validity (Goodman, 2001).

Conclusion

In this population-based study exploring the potential effect of binge drinking in the time span before most women have recognized their pregnancy, binge exposure predicted an Abnormal and Borderline score on the SDQ Total, Emotional symptoms, Conduct problems, and Hyperactivity/Inattention in 5.5-year-old children. Very early binge exposure was a stronger predictor than maternal depression or infant birth weight and had a direct effect on the symptom scores. Reporting a higher level of binge drinking (≥8 SUpo) had stronger predictive power than reporting 5 to 7 SUpo. After removal of those reporting higher level of binge, very early binge exposure still predicted high symptom scores. The results were not explained by participants reporting major lifetime depression.

Acknowledgments

We are indebted to all the participating women and grateful to the staff at the Antenatal Outpatient Clinic at Ullevaal University Hospital for recruitment of participants to the study. Grants are from Sogn Centre for Child and Adolescent Psychiatry, University of Oslo, and The Norwegian Council for Mental Health/The Norwegian ExtraFoundation for Health and Rehabilitation through EXTRA funds. These study sponsors had no involvement in the study design, in the collection, analysis or interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.

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