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Keywords:

  • Binge drinking;
  • intelligence;
  • IQ;
  • neurodevelopmental effects;
  • prenatal exposure;
  • WPPSI-R

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

Please cite this paper as: Kesmodel U, Falgreen Eriksen H, Underbjerg M, Kilburn T, Støvring H, Wimberley T, Mortensen E. The effect of alcohol binge drinking in early pregnancy on general intelligence in children. BJOG 2012;119:1222–1231.

Objective  To examine the effects of binge alcohol consumption during early pregnancy, including the number of binge episodes and the timing of binge drinking, on general intelligence in 5-year-old children.

Design  Follow-up study.

Setting  Neuropsychological testing in four Danish cities 2003–2008.

Population  A cohort of 1617 women and their children sampled from the Danish National Birth Cohort.

Methods  Participants were sampled on the basis of maternal alcohol consumption during pregnancy. At 5 years of age the children were tested with six subtests from the Wechsler Preschool and Primary Scale of Intelligence – Revised (WPPSI-R). Parental education, maternal IQ, prenatal maternal smoking, the child’s age at testing, the gender of the child, and tester were considered core confounding factors, whereas the full model also controlled for prenatal maternal average alcohol intake, maternal age, maternal pre-pregnancy body mass index (BMI), parity, home environment, postnatal parental smoking, health status, and indicators for hearing and vision impairment.

Main outcome measure  WPPSI-R.

Results  There were no systematic or significant differences in general intelligence between children of mothers reporting binge drinking and children of mothers with no binge episodes, except that binge drinking in gestational weeks 1–2 significantly reduced the risk of low, full-scale IQ (OR 0.54; 95% CI 0.31–0.96) when adjusted for core confounding factors. The results were otherwise not statistically significantly related to the number of binge episodes (with a maximum of 12) and timing of binge drinking.

Conclusions  We found no systematic association between binge drinking during early pregnancy and child intelligence. However, binge drinking reduced the risk of low, full-scale IQ in gestational weeks 1–2. This finding may be explained by residual confounding.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

High maternal alcohol intake during pregnancy has been suggested as one of the leading preventable causes of mental retardation.1,2

An intake of two or three alcoholic drinks per day has been associated with lower general intelligence compared with no intake,3 whereas an intake of low, weekly quantities of alcohol has not been consistently associated with low intelligence.3–6

In animal models, the peak blood alcohol concentration (BAC) rather than average intake seems to determine the level of damage.7 Brain growth is particularly susceptible to high BACs.8 A few studies in humans suggest that binge drinking during pregnancy may be associated with poor neurodevelopmental outcomes.9,10 Whereas only a few pregnant women drink alcohol on a daily basis, 40–50% of pregnant women in Denmark admit to isolated episodes of binge drinking (five or more drinks on a single occasion), particularly before realising that they were pregnant.11

In a few studies, consistent binge drinking throughout pregnancy has been associated with lower intelligence, but it has been difficult to separate this effect from the effect of an associated high daily intake.10 A few small studies have assessed the effect of isolated episodes of binge drinking, but the results are inconsistent, and none seem to have included analyses of the number or the timing of binge episodes.6,12–15

We aimed to carry out a large-scale study of the potential effects of maternal binge drinking during pregnancy, including the number and timing of binge episodes, on psychometric intelligence (IQ), as measured by standardised tests of intelligence in 5-year-old children.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

The design of the Lifestyle During Pregnancy Study (LDPS) has been described in detail elsewhere.16 Briefly, the study is a prospective follow-up, based on a sample from the Danish National Birth Cohort (DNBC),17 with oversampling of moderate to high alcohol exposure categories, including binge drinking.16

The DNBC consists of 101 042 women and their children, recruited from 1997 to 2003 at their first antenatal visit. Participants were sampled from the DNBC in strata defined by the prenatal maternal average alcohol intake (0, 1–4, 5–8, and ≥9 drinks/week) and timing of binge episodes, defined as five or more drinks on one occasion (none, gestational weeks 1–2, 3–4, 5–8, or ≥9).18 The higher exposure categories were oversampled in an effort to ensure that all exposure categories included enough children to attain sufficient statistical power. A total of 3478 women with singleton pregnancies and their children were sampled from the DNBC and invited to participate in the LDPS between 2003 and 2008.16 Women sampled on the basis of pre-pregnancy alcohol intake were not included in the analyses presented here (n = 289), and 18 women did not have valid information on binge drinking, leaving 3171 women invited, 1617 of whom were tested. Only these mother and child pairs were included in the analyses.

Exclusion criteria for the LDPS were: inability to speak Danish; impaired hearing or vision in the child, to the extent that the test session could not be performed; multiple pregnancies; and congenital diseases likely to cause mental retardation (e.g. trisomy 21).

Data collection

Exposure assessment

The information on alcohol consumption during the index pregnancy was extracted from the interview performed with all women included in the DNBC (median, 17 weeks of gestation; range 7–39 weeks of gestation).18 The information included data on the number of binge episodes (i.e. an intake of five or more drinks on a single occasion), and the timing (gestational week) of these episodes. Additional questions assessed the average number of drinks per week of beer, wine, and spirits that the woman consumed currently at the time of the prenatal interview, as well as before pregnancy (see Eriksen et al. for details).5 The definition of a drink followed the definition from the Danish National Board of Health, with one standard drink being equal to 12 g of pure alcohol. Analyses of the effects of the average number of drinks per week on IQ in children are described in a separate article.5

The 5-year follow-up

Selected mothers were invited to participate in the study by letter 4–6 weeks (mean, 5.8 weeks; SD, 0.7 weeks) before their child’s fifth birthday. A self-administered questionnaire for the parents regarding the child’s general postnatal health and development, as well as maternal and paternal postnatal lifestyles, was mailed to the participants.

When the child was between 60 and 64 months old, a 3-hour assessment was carried out in one of four test sites,16 comprising a comprehensive neuropsychological test battery administered by a psychologist.

Test procedures were standardised in detail and carried out by ten trained psychologists blinded to the child’s exposure status.

Outcome measures

Intelligence was assessed with the Wechsler Primary and Preschool Scales of Intelligence – Revised (WPPSI-R),19 one of the most widely used standardised tests of intelligence for children of 2–7 years of age. The WPPSI-R comprises five verbal subtests and five performance (non-verbal) subtests, from which verbal (VIQ), performance (PIQ), and full-scale (FSIQ) IQs are derived.

To reduce the length of the test session, we used a short form including three verbal (arithmetic, information and vocabulary) and three performance (block design, geometric design, and object assembly) subtests. Standard procedures were used to assess IQs from the shortened forms of the tests.19

No Danish WPPSI-R norms were available at the time of the study, so Swedish norms were used to derive scaled scores and IQs. Because Swedish norms were used and because of the stratified sampling according to alcohol exposure, the theoretical distribution of IQ with a mean of 100 and an SD of 15 cannot be expected in this sample, but this will not affect internal comparisons within the sample with respect to alcohol exposure.

Statistical analysis

Covariates

The following covariates were obtained in the prenatal interview: prenatal maternal average alcohol intake; parity; prenatal smoking; and maternal pre-pregnancy BMI. At the time of the 5-year follow-up, the following variables were recorded: maternal marital status; parental education in years; an index of the quality of postnatal home environments; and an index of the child’s health status. The coding of the included covariates is described in detail elsewhere.5

Maternal IQ was assessed at the follow-up examination: two verbal subtests (information and vocabulary) from the Wechsler Adult Intelligence Scale (WAIS) assessed VIQ,20 and the Raven’s Standard Progressive Matrices provided non-VIQ.21 Raw scores of each test were standardised based on the results from the full sample, and were weighted equally in a combined score that was restandardised to an IQ scale with a mean of 100 and an SD of 15.

Maternal age was obtained directly from the unique Danish personal identification number, as was the gender and age of the child at testing. Birthweight (g) and gestational age (days) were obtained from the Danish Birth Registry.

All statistical analyses were conducted in Stata 11 (StataCorp LP, College Station, TX, USA) and weighted by sampling probabilities,22 with robust variance estimation. All statistical tests were two-sided and declared significant at a level of 5%. All estimates are accompanied by 95% confidence intervals.

Missing information

The number of missing values in each variable ranged from two to 33, with eight missing values on FSIQ. Missing values were imputed based on two strategies: a dedicated model for imputations; and a black-box strategy.5 For both strategies 100 completed data sets were generated. Regardless of strategy, the main conclusions were unaffected. The point estimates never differed by more than 3% relative to their standard error. Essentially the same results were obtained when the complete case analysis was used. In this paper, we only report results based on the dedicated imputation strategy. All imputations were implemented with the ice add-on command, and the built-in mi estimate command of Stata 11.

Data analyses

Separate analyses were performed for the effects of binge drinking as a dichotomous variable (yes/no), number of binge episodes (continuous, coded as 0, 1, 2, and ≥3), and timing of binge drinking (none, gestational weeks 1–2, 3–4, 5–8, and ≥9, multiple timings). The associations with the continuous FSIQ, VIQ, and PIQ outcome scores were estimated using multiple linear regression. Parental education, maternal IQ, prenatal maternal smoking, the child’s gender and age at testing and tester were considered core confounding factors in a separate model. The final model, in addition, included parity, maternal marital status, maternal age, BMI, prenatal maternal average number of drinks per week, home environment, postnatal parental smoking, health status, hearing and vision abilities. As birthweight and gestational age could be considered potential mediators of an effect of alcohol, analyses including these two variables in the full model were also performed. Results did not differ substantially from analyses without the variables, and are therefore not reported here.

Additionally, we analysed the three IQ outcomes dichotomised using the sample mean – 1 SD as the cut-off for subnormal FSIQ, VIQ, and PIQ. Logistic regressions were used in these analyses, using odds ratios, with the category of IQ above the cut-off as the reference group.

We also analysed the raw scores of each individual WPPSI-R subtest with linear regression models, adjusting for core and all confounding factors. Potential interactions with binge drinking were assessed for gender of the child, parental education, prenatal maternal average alcohol exposure and maternal smoking during pregnancy.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

Table 1 presents unadjusted sample characteristics. Women engaging in binge drinking were more likely to be slightly younger, primiparous, smokers both before and after pregnancy, and had a lower body mass index (BMI), a higher average alcohol intake and a higher IQ compared with non-bingers. No substantial differences were seen between participants and non-participants (Table 2). The number of binge episodes reported in early pregnancy did not vary with time of interview.

Table 1.   Sample characteristics,* across number of alcohol binge episodes,** during pregnancy
 Number of binge drinking episodes during pregnancy P
012≥3***Total
  1. *Based on unweighted data. P values based on weighted analyses.

  2. **Defined as an intake of five drinks or more on one occasion.

  3. ***Range: 3–12 episodes.

  4. ****Single if reported as being single either in pregnancy or at follow-up (60–64 months postpartum).

  5. *****Defined as a score on at least two of the following items: single parent household; changes in care giving; daycare of more than 8 hours per day before the age of 3 years; 14 + days away from home; irregular breakfast meals; maternal depression; high maternal or paternal alcohol use.

  6. ******Range: 9–14 drinks/week.

  7. *******Medical conditions or regular medications that may influence test performance.

Number of participants 4957832251141617 
Sampling fraction 1.5 (1.2/34.3)13.8 (5.2/49.6)8.0 (5.2/49.6)8.0 (5.5/57.9)9.7 (1.5/49.6) 
Timing of interview (gestational week) 17 (13/23)17 (13/24)17 (13/24)17 (13/24)17 (13/24)0.46
Family characteristics
Maternal age, years (mean ± SD) 31.4 ± 4.530.5 ± 4.330.8 ± 4.431.4 ± 4.130.9 ± 4.40.02
Parity
0 (%)42.851.057.364.950.3<0.01
1 (%)36.232.127.122.832.0
≥2 (%)21.017.015.612.317.7
Maternal pre-pregnancy BMI, kg/m2 (median, 10th/90th percentiles) 22.8 (19.6/29.0)22.7 (19.6/28.7)22.2 (19.4/26.9)22.3 (20.0/30.5)22.6 (19.6/28.7)<0.01
Maternal marital status****
Single (%)9.814.110.411.512.10.42
Parental education, years (median, 10th/90th percentiles) 13.0 (11.0/16.0)13.0 (11.0/16.0)13.0 (11.0/16.0)13.0 (11.0/16.5)13.0 (11.0/16.0)0.15
Family/home index
Suboptimal (%)*****17.020.216.718.418.60.20
Maternal IQ (mean ± SD) 98.9 ± 15.9100.1 ± 14.4100.6 ± 14.3103.3 ± 14.8100.0 ± 14.90.01
Maternal prenatal smoking
Smokers (%)25.530.938.246.531.4<0.01
Postnatal parental smoking
Smokers (%)26.533.734.239.532.00.01
Average prenatal alcohol consumption
0 drinks/week (%)51.546.542.236.846.8<0.01
1–4 drinks/week (%)30.945.549.346.541.6
5–8 drinks/week (%)15.28.07.614.010.6
≥9 drinks/week (%)******2.40.92.61.1
Gender
Male (%)54.351.148.954.452.00.56
Age at testing in years (median, 10th/90th percentiles) 5.2 (5.1/5.3)5.2 (5.1/5.3)5.2 (5.1/5.3)5.2 (5.1/5.3)5.2 (5.1/5.3)0.24
Birthweight, grams (mean ± SD) 3633.1 ± 574.53592.0 ± 488.53586.3 ± 501.83561.5 ± 476.83601.7 ± 517.50.54
Gestational age, days(median, 10th/90th percentiles) 281 (268/293)281 (266/293)282 (270/293)282 (270/293)281 (267/293)0.13
Health status condition/medicine (%)******* 2.44.02.23.53.20.98
Hearing abilities
Normal (%)94.196.594.294.795.40.50
Vision abilities
Normal (%)98.096.796.996.597.10.74
Table 2.   Maternal and child characteristics of participants and non-participants
 ParticipantsQuestionnaire onlyNon-participantsTotal
  1. *Defined as an intake of five or more drinks on one occasion.

  2. **Range: 3–12 episodes.

Number of participants 161714014143171
Sampling fraction 9.7 (1.5/49.6)9.7 (1.2/34.3)8.0 (1.5/49.6)8.0 (1.5/49.6)
Timing of interview (gestational week) 17.0 (13.0/24.0)18.0 (13.0/23.0)17.0 (13.0/24.0)17.0 (13.0/24.0)
Maternal characteristics
Age, years (mean ± SD) 30.9 ± 4.430.5 ± 4.730.2 ± 4.630.6 ± 4.5
Prenatal marital status
Single (%)3.01.43.13.0
Parity
0 (%)50.352.948.849.8
1 (%)32.031.433.232.5
2 (%)17.715.717.817.7
Maternal pre-pregnancy BMI, kg/m2 (median, 10th/90th percentiles) 22.6 (19.6/28.7)22.7 (19.5/28.0)23.0 (19.4/30.1)22.8 (19.5/29.1)
Smoking in pregnancy
Smokers (%)31.428.135.032.8
Number of binge drinking episodes during pregnancy*
030.636.434.732.7
148.442.946.047.1
213.915.712.413.3
≥3**7.15.06.96.9
Gender
Male (%)52.049.351.451.6
Birthweight, grams (mean ± SD) 3601.7 ± 517.53586.4 ± 524.33542.7 ± 559.13574.7 ± 537.4
Gestational age at birth, days (median, 10th/90th percentiles) 281.0 (267.0/293.0)281.0 (265.0/292.0)281.0 (264.0/293.0)281.0 (266.0/293.0)

For mean FSIQ, unadjusted analyses showed a small but significant increase in IQ with increasing number of binge episodes (Table 3, = 0.01). For two or more binge episodes the difference was approximately three IQ points (Table 3). However, when adjusting for potential confounding, no significant or clinically relevant differences were observed (Table 3). No significant or clinically relevant differences were observed for timing of binge drinking or the dichotomous binge variable and FSIQ in any analyses (Table 3).

Table 3.   Associations between maternal binge drinking in pregnancy and offspring mean WPPSI-R FSIQ, Denmark, 2003–2008
 CrudeAdjusted for core confounding factors*Adjusted for potential confounding factors**
Mean scoreMean difference95% CIMean difference95% CIMean difference95% CI
  1. *Parental education, maternal IQ, prenatal maternal smoking, age at testing, gender of child, and tester.

  2. **Parental education, maternal IQ, prenatal maternal smoking, prenatal maternal average alcohol intake, maternal age, parity, prenatal and postnatal marital status, postnatal parental smoking, maternal pre-pregnancy BMI, gender of child, age at testing, health status, hearing and vision on the day of testing, family/home environment, and tester.

  3. ***P value for the hypothesis of no difference in IQ scores across levels of average alcohol intake.

  4. ****Range: 3–12 episodes.

Binge drinking in pregnancy
No104.97ReferenceReferenceReference
Yes106.291.32−0.30; 2.950.30−1.09; 1.700.04−1.43; 1.51
P***0.110.670.96
Number of binge drinking episodes in pregnancy
0104.97ReferenceReferenceReference
1105.340.38−1.37; 2.13−0.36−1.89; 1.16−0.56−2.14; 1.02
2108.043.080.84; 5.321.50−0.49; 3.501.06−1.06; 3.18)
≥3****108.003.030.10; 5.961.61−1.07; 4.291.49−1.21; 4.19
P***0.010.180.27
Timing of binge drinking episodes in pregnancy (gestational week)
No binge drinking104.97ReferenceReferenceReference
1–2106.982.01−0.07; 4.090.61−1.22; 2.440.30−1.60; 2.19
3–4105.530.56−1.63; 2.76−0.63−2.56; 1.31−1.00−3.01; 1.02
5–8106.901.94−0.25; 4.120.83−1.14; 2.810.70−1.31; 2.70
≥9104.31−0.66−2.76; 1.45−0.33−2.32; 1.66−0.10−2.21; 2.02
Multiple episodes107.162.20−0.17; 4.571.44−0.70; 3.591.26−0.97; 3.48
P***0.060. 500.55

For VIQ, two binge episodes versus none were associated with a small, unadjusted increment in IQ of 2.35 IQ points (95% CI 0.46–4.25). Otherwise no significant or clinically relevant differences were observed for any of the binge variables in the unadjusted (data not shown) or the adjusted analyses of VIQ and PIQ (Table 4).

Table 4.   Associations between maternal binge drinking in pregnancy and offspring mean WPPSI-R VIQ and PIQ, Denmark, 2003–2008, adjusted for core confounding factors*
 VIQPIQ
Mean score (crude)Mean difference95% CIMean score (crude)Mean difference95% CI
  1. *Parental education, maternal IQ, prenatal maternal smoking, age at testing and gender of child, and tester.

  2. **P value for the hypothesis of no difference in IQ scores across levels of binge drinking.

  3. ***Range: 3–12 episodes.

Binge drinking in pregnancy
No104.73Reference104.06Reference
Yes105.35−0.05−1.25; 1.16105.770.54−1.28; 2.37
P**0.940.56
Number of binge drinking episodes in pregnancy
0104.73Reference104.06Reference
1104.44−0.70−1.99; 0.58105.010.02−1.96; 2.00
2107.081.34−0.42; 3.09107.161.28−1.29; 3.85
≥3***106.930.86−1.62; 3.35107.161.94−1.37; 5.25
P**0.100.51
Timing of binge drinking episodes in pregnancy (gestational week)
No binge drinking104.73Reference104.06Reference
1–2105.31−0.43−1.88;1.19107.151.50−0.92; 3.92
3–4104.85−0.73−2.40; 0.89104.93−0.36−2.81; 2.09
5–8105.730.37−1.07; 2.17106.310.68−2.10; 3.46
≥9103.18−0.90−2.57; 0.82104.500.30−2.33; 2.93
Multiple episodes106.591.18−0.68; 3.21106.001.20−1.45; 3.86
P**0.300.74

For dichotomised FSIQs there was a pattern of reduced risk of low FSIQ with all binge patterns (Table 5). After adjusting for core confounding factors, one result remained significant in the analyses: binge drinking in gestational weeks 1–2 significantly reduced the risk of low FSIQ (OR 0.54; 95% CI 0.31–0.96).

Table 5.   Associations between maternal binge drinking in pregnancy and low WPPSI-R FSIQ (< −1 SD), Denmark 2003–2008
  CrudeAdjusted for core confounding factors*Adjusted for potential confounding factors**
Odds ratio95% CIOdds ratio95% CIOdds ratio95% CI
  1. *Parental education, maternal IQ, prenatal maternal smoking, age at testing and gender of child, and tester.

  2. **Parental education, maternal IQ, prenatal maternal smoking, prenatal maternal average alcohol intake maternal age, parity, prenatal and postnatal marital status, postnatal parental smoking, maternal pre-pregnancy BMI, gender of child, age at testing, health status, hearing and vision on the day of testing, family/home environment, and tester.

  3. ***P value for the hypothesis of no difference in IQ scores across levels of average alcohol intake.

  4. ****Range: 3–12 episodes.

Binge drinking in pregnancy
NoReferenceReferenceReference
Yes0.660.47; 0.910.740.52; 1.070.770.53; 1.12
P***0.010.110.18
Number of binge drinking episodes in pregnancy
0ReferenceReferenceReference
10.770.54; 1.090.850.57; 1.260.860.58; 1.29
20.460.26; 0.820.570.31; 1.060.610.33; 1.16
≥3****0.440.21; 0.920.500.22; 1.130.530.23; 1.25
P***0.020.170.30
Timing of binge drinking episodes in pregnancy (gestational week)
No binge drinkingReferenceReferenceReference
1–20.440.26; 0.750.540.31; 0.960.560.31; 1.01
3–40.770.50; 1.210.900.55; 1.490.930.55; 1.55
5–80.620.38; 1.010.700.40; 1.230.690.39; 1.23
≥90.830.53; 1.300.770.45; 1.320.770.44; 1.35
Multiple episodes0.630.37; 1.060.680.38; 1.220.750.41; 1.37
P***0.040.330.44

All adjusted analyses of binge drinking and low VIQ and PIQ were statistically insignificant (Table 6).

Table 6.   Associations between maternal binge drinking in pregnancy and low WPPSI-R VIQ and PIQ (<−1 SD), Denmark, 2003–08, adjusted for core confounding factors*
 VIQPIQ
Odds ratio95% CIOdds ratio95% CI
  1. *Parental education, maternal IQ, prenatal maternal smoking, age at testing and gender of child, and tester.

  2. **P value for the hypothesis of no difference in IQ scores across levels of binge drinking.

Binge drinking in pregnancy
NoReferenceReference
Yes0.910.62; 1.331.000.70; 1.42
P**0.630.98
Number of binge drinking episodes in pregnancy
0ReferenceReference
11.030.69; 1.541.050.72; 1.53
20.590.31; 1.140.830.48; 1.45
≥30.850.38; 1.921.030.53; 1.99
P**0.380.87
Timing of binge drinking episodes in pregnancy (gestational week)
No binge drinkingReferenceReference
1–20.900.51; 1.570.780.47; 1.31
3–41.040.62; 1.751.100.68; 1.77
5–80.660.35; 1.221.220.75; 1.99
≥91.250.74; 2.130.840.50; 1.42
Multiple episodes0.760.41; 1.420.950.56; 1.62
P**0.490.69

For VIQ, the interaction between the number of binge episodes and an average alcohol intake of four or more drinks per week was significant (= 0.02 and 0.04 when adjusting for core confounding factors and all confounding factors, respectively): for women reporting drinking four or fewer drinks per week, one binge episode was associated with a small reduction in VIQ, whereas two and three or more binge episodes were associated with higher VIQs. For women drinking more than four drinks per week, both one binge episode and three or more binge episodes were associated with higher VIQs, whereas two binge episodes were associated with a reduction in VIQ. Hence, no biologically plausible pattern was evident in the stratified analyses. For PIQ, the interaction between the timing of binge episodes and gender was significant (= 0.02) when adjusting for core confounding factors. Here, there was a tendency towards slightly but insignificantly lower PIQs in girls exposed to binge drinking from gestational week 3 onwards, whereas boys had systematically higher PIQs in all gestational periods compared with the sons of non-bingers. No interactions were seen with respect to prenatal maternal smoking or parental education.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

Overall, we found no systematic associations between binge drinking during early pregnancy and intelligence in children. Two or more maternal binge episodes in early pregnancy were consistently associated with insignificantly higher IQ and a lower risk of low IQ on both FSIQ, VIQ, and PIQ in both adjusted and unadjusted analyses. Binge drinking in gestational weeks 1–2 was associated with a significant reduction in the risk of low FSIQ in crude analyses and when controlling for core confounding factors, but not after controlling for all potential confounding factors.

Previous studies on binge drinking and IQ have – with one exception – generally been on a small scale. Bailey et al.12 (= 499, children assessed at 5.9–7.9 years of age) found a significantly negative association between binge drinking and VIQ (= 0.014) after controlling for family socio-economic status, home environment, maternal smoking in pregnancy, cocaine use, and exposure of the child to violence. No effect was seen on PIQ or FSIQ.

Sayal et al.15 (= 924, children assessed at age 49 months), Nulman et al. 14 (= 102, children of diverse but unknown ages), and Chiodo et al.13 (= 75, children assessed at age 4–5 years) found no significant effects of binge drinking on IQ.

O’Callaghan et al.6 reported on a substantially larger sample than previous studies (= 3731, assessed at 14 years of age). They reported a significantly increased risk of low IQ, defined as a Raven score < 85 (OR 1.4; 95% CI 1.1–1.8), in children of women who reported binge drinking for less than half the time they drank alcohol. Yet no effect was seen for women reporting more intense binge drinking, i.e. more than half the time when they drank alcohol (OR 1.1; 95% CI 0.6–2.1).6 Although the finding is interesting, it seems biologically implausible.

Overall, we found mostly unsystematic and insignificant associations, in line with our findings in multivariate analyses reported elsewhere.22 The few significant and systematic findings seemed to be in the opposite direction of what would have been expected. There are several potential explanations for such findings.

First, it may reflect a true, biological association: in rats, small quantities of alcohol during the pre-implantation period may advance the time course of blastocyst implantation without reducing fecundity.23 If this is true in humans, alcohol intake during weeks 1–2 immediately before implantation might do the same thing, if the time spent in utero (i.e. from implantation to birth) positively affects IQ.24 Small weekly quantities of alcohol have been shown to be associated with longer gestations and reduced risk of preterm delivery.25,26 However, the unadjusted increase in FSIQ was 0.11 (0.02–0.20) points per day of longer gestation, and we find it unlikely that this small effect could explain our finding.

Second, it may be the result of random error. Considering the number of statistical analyses performed, a few chance findings may be expected. Third, although selection bias cannot be ruled out completely, it is unlikely, as the characteristics of participants and non-participants did not differ substantially. Still, although selection is likely in the DNBC, and further selection has taken place in this study, the differential participation in the DNBC seems to cause only little if any bias in studies within the DNBC.27

With regard to potential information bias, our study has several strengths. IQ was assessed by a state-of-the-art clinical intelligence test. The measurements of alcohol intake were based on structured interviews, and this particular method has been shown to yield valid (relative to other methods) and reliable information among pregnant Danish women.8,28 Furthermore, in Denmark weekly alcohol consumption during pregnancy is considered acceptable,29 reducing the risk of the systematic under-reporting of alcohol intake.

None of the previous studies addressed the issues of the number of binge episodes and the timing of binge drinking.

Still, the blood concentration depends not only on the volume of alcohol consumed, but also on the time spent drinking, as well as the blood volume and speed of enzymatic breakdown. Thus, our estimates are likely to be conservative estimates. Also, the complete denial of alcohol intake by at-risk drinkers cannot be ruled out.

Potential damage caused by alcohol could depend on the timing of alcohol intake. Yet no further stratification was performed from gestational week 9 onwards. If potential effects of binge drinking occur mainly within a short period of time in the late second or third trimester, when the central nervous system is still developing, our study could not assess such a risk.

The stability of cognitive test scores may be a problem in children aged 4–5 years, but the reliability coefficients for the present age group are very high for the IQs derived by WPPSI-R (0.90–0.96). Effects of alcohol on IQ observed in early childhood have been found to be insignificant at follow-ups in later childhood and adolescence, and consequently, long-term effects cannot necessarily be predicted from findings in early childhood. In principle, early deficits may grow more pronounced, but the dilution of early effects seems to be more common. Thus, we find it unlikely that a future follow-up of our sample would show any effects of binge drinking.

The time span between exposure and outcome assessment implies that other exposures and developmental factors may influence the outcome. We adjusted for a number of such potential confounding factors, but showed no relevant evidence of any association between binge drinking and child IQ, except during gestational weeks 1–2.

We included critical confounding factors, particularly maternal IQ and parental education. Education has been shown to account for 19% of the variance in IQ.4 Maternal IQ and home environment have been shown to account for 25–29% of the variance.30 Yet, none of the previous studies adjusted for all of these confounding factors. We found that women reporting no binge episodes had lower IQ than women reporting any number of binge episodes (Table 1). Maternal education, smoking status, parity, age, and average alcohol intake have previously been shown to be strongly associated with binge drinking, both in the DNBC and independent samples.11,31

When assessing average IQ in this study, there was a tendency towards weaker associations with an increasing number of potential confounding factors included in the analyses, suggesting room for unadjusted confounding from variables not included in the analyses. Still, this pattern was not equally apparent when assessing the risk of low IQ.

The finding that small quantities of alcohol may appear to be beneficial has previously been shown in studies on preterm birth,25 low birthweight,32 and in the long-term follow-up of cognitive function and behaviour.33,34 Although a potentially biological effect cannot be ruled out, the denial of alcohol consumption by risk drinkers and residual confounding are likely explanations for such findings.

In summary, in this large-scale study we found mostly unsystematic and insignificant associations between binge drinking during early pregnancy and child intelligence, even after adjustment for maternal intelligence and a wide set of other potential confounding factors. The few significant findings seemed to be in the opposite direction to what would have been expected. Although such findings may well be explained by unadjusted confounding, we found no evidence of lower IQ in the children of women with a few episodes of binge drinking.

Contribution to authorship

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

USK, MU, TK, and ELM contributed to the design of the Lifestyle During Pregnancy Study. USK wrote the first draft of the article, and HS and TW were responsible for the statistical analyses. All authors contributed to the interpretation of the results, and provided critical comments and revisions of the article.

Details of ethics approval

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

The study was approved by the DNBC Board of Directors, the DNBC Steering Committee, the Regional Ethics Committee, the Danish Data Protection Agency, and the Institutional Review Board at the Centers for Disease Control and Prevention. Signed informed consent was obtained for the LDPS.

Funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

This study was supported primarily by the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA. Additional support was obtained from The Danish National Board of Health, the Lundbeck Foundation, Ludvig & Sara Elsass’ Foundation, the Augustinus Foundation, and Aase & Ejnar Danielsen’s Foundation.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References

The Danish National Research Foundation has established the Danish Epidemiology Science Center that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Foundation.

The authors would like to thank all of the participants for their time and effort, as well as Dr Poul Thorsen for his contribution to initiating the Lifestyle During Pregnancy Study.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. Acknowledgements
  12. References
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