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Aim The aim of this study was to examine the association between maternal alcohol use disorder and intellectual disability in children.
Method All mothers with an International Classification of Diseases (ICD) 9 and/or 10 alcohol-related diagnosis, a proxy for alcohol use disorder, recorded on the Western Australian health, mental health, and drug and alcohol data sets were identified through the Western Australian Data Linkage Unit (n=5614 non-Aboriginal; n=2912 Aboriginal). A comparison cohort of mothers without an alcohol-related diagnosis was frequency matched on maternal age within maternal Aboriginal status and year of birth of their children. Linkage with the Western Australian Midwives Notification System (1983–2001) identified all births to these mothers (n=10 664 and 7907 respectively). Linkage to the Western Australian Intellectual Disability Database and Register of Developmental Anomalies identified cases of intellectual disability with no identified genetic origin (intellectual disability) (n=1487) and fetal alcohol syndrome (n=66). Odds ratios (ORs) and 95% confidence intervals (CIs) for intellectual disability were calculated using logistic regression incorporating generalized estimating equations and used to estimate population-attributable fractions.
Results At least 3.8% (95% CI 2.84–4.89%) of cases of intellectual disability could be avoided by preventing maternal alcohol use disorder: 1.3% (95% CI 0.81–1.86%) in non-Aboriginal and 15.6% (95% CI 10.85–20.94%) in Aboriginal children. We observed a three-fold increase in the adjusted odds of intellectual disability in children of mothers with an alcohol-related diagnosis recorded during pregnancy (non-Aboriginal OR 2.89, 95% CI 1.62–5.18; Aboriginal OR 3.12, 95% CI 2.13–4.56), with a net excess proportion of 3.7% and 5.5% respectively. One-third (32%) of children diagnosed with fetal alcohol syndrome had intellectual disability.
Interpretation Maternal alcohol use disorder is the leading known risk factor for intellectual disability with no identified genetic origin.
‘Fetal Alcohol Syndrome (FAS) is the leading non-genetic cause of intellectual disability.’1 This statement rapidly became the catchcry following Abel and Sokol’s publications in the late 1980s.1,2 The authors estimated that the worldwide incidence of FAS was 1.9 cases per 1000 live births, and they postulated that FAS-related intellectual disability accounted for 11% of institutional costs for intellectually disabled residents in the USA.2 Yet this statement has never been ratified using population-based research, and the contribution of maternal alcohol use disorder to the burden of intellectual disability remains unknown.
The assumption appears to be that all children with FAS have intellectual disability. However, the current evidence does not support this. A wide range of IQs has been observed in children with FAS and broader fetal alcohol spectrum disorders (FASDs).3–8 The mean IQ of individuals with FAS is reported to be around 68–70, with one-third classified as intellectually disabled (IQ<70).7,8 Intellectual disability is only one of a wide range of fetal effects classified as FASDs. Based on evidence from school-based studies, the highest documented prevalence of FAS and partial FAS ranges from 2% to 5%.9 The prevalence of alcohol-related neurodevelopmental disorder (ARND)10 is more difficult to ascertain since the characteristic FAS facial features are absent. Estimates of the prevalence of ARND are considerably higher than for FAS or partial FAS.9 Although the mean IQ of children with FASD in these studies was lower than in children with ARND (mean IQ 85 and 109 receptively), the prevalence of intellectual disability and the attributable fractions were not documented.9 These knowledge gaps have critical implications for health professionals, who are unable to advise what percentage of children prenatally exposed to heavy levels of alcohol will have an intellectual disability.
Ascertaining population-based estimates of the proportion of intellectual disability that can be attributed to maternal alcohol use disorder occurring during pregnancy is problematic. In the absence of the characteristic FAS dysmorphology, prenatal alcohol exposure may not be identified as a contributing cause of intellectual disability in children. This is likely to be the case in Australia, where pregnant mothers are not routinely asked about alcohol consumption during pregnancy,11 health professionals lack knowledge about FAS,11,12 and women who consume high levels of alcohol are difficult to retain in longitudinal studies.13
The present study overcomes these limitations by using linked, routinely collected population-based data to examine the association between the presence of an alcohol-related diagnosis in maternal health data sets, a proxy for maternal alcohol use disorder, and the presence of an intellectual disability with no identified genetic origin in the children of the identified mothers.
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- What this paper adds
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There were 64 842 children in the study; 41 320 (63.7%) of the children were non-Aboriginal, of whom 10 576 (25.6%) had a mother with an alcohol-related diagnosis; 23 522 (36.3%) were Aboriginal, of whom 7 760 (33.0%) had a mother with an alcohol-related diagnosis (Table I). Exposed mothers were less likely than comparison mothers to be married, and more likely to be of higher parity, have a mental health diagnosis, or have a diagnosis of illicit drug use. The majority of non-Aboriginal mothers in both the exposed and comparison cohorts lived in Perth (72.2%), with the majority of Aboriginal mothers living in rural/remote Western Australia (69.6%) at the time of birth of their child (Table I).
Table I. Maternal demographic characteristics by Aboriginal status, for each live birth between 1983 and 2001
| ||Non-Aboriginal births (n=41 320)||Aboriginal births (n=23 522)|
|Exposed (n=10 576), n (%)||Comparison (n=30 744), n (%)||Exposed (n=7760), n (%)||Comparison (n=15 762), n (%)|
|Maternal age (y)|
| <20||1377 (13.0)||4024 (13.1)||2297 (29.6)||4238 (26.9))|
| 20–24||3284 (31.1)||9514 (30.9)||2681 (34.5)||5605 (35.5)|
| 25–29||3184 (30.1)||9199 (29.9)||1686 (21.7)||3624 (23.0)|
| 30–34||1895 (17.9)||5542 (18.0)||806 (10.4)||1667 (10.6)|
| 35–39||707 (6.7)||2111 (6.9)||266 (3.4)||559 (3.5)|
| 40+||129 (1.2)||354 (1.2)||24 (0.3)||69 (0.4)|
| Married||7757 (73.5)||26 286 (85.5)||4377 (56.6)||10 065 (64.0)|
| Never married||2395 (22.7)||4179 (13.6)||3212 (41.5)||5424 (34.5)|
| Divorced/widowed||401 (3.8)||269 (0.9)||144 (1.9)||229 (1.5)|
| 0||4168 (39.4)||15 087 (49.1)||1989 (25.6)||4646 (29.5)|
| 1||3214 (30.4)||9618 (31.3)||1758 (22.7)||3797 (24.1)|
| 2||1863 (17.6)||4115 (13.4)||1527 (19.7)||2949 (18.7)|
| 3+||1331 (12.6)||1924 (6.3)||2486 (32.0)||4370 (27.7)|
| Illicit drug use||5343 (38.3)||608 (1.5)||2226 (22.4)||979 (4.7)|
| Schizophrenia||473 (4.5)||88 (0.3)||309 (4.0)||119 (0.8)|
| Depression||3223 (30.5)||948 (3.1)||974 (12.6)||749 (4.7)|
| All other diagnoses||5171 (48.9)||2239 (7.3)||2081 (26.8)||1624 (10.3)|
|Health region of WA|
| Perth metropolitan||7625 (72.1)||21 809 (70.9)||2210 (28.5)||4887 (30.9)|
| Rural/remote WA||2895 (27.4)||8675 (28.2)||5535 (71.3)||10 824 (68.7)|
| Outside WA||56 (0.5)||260 (0.8)||15 (0.2)||51 (0.3)|
Intellectual disability was diagnosed in 1660 children. A genetic/chromosomal cause was identified for 169 children in the IDEA database, and for a further four children a chromosomal cause was identified from linkage to the Western Australian Register of Developmental Anomalies (British Paediatric Association Codes 75800–75899). This equated to 10.4% of all intellectual disability in this cohort having a known genetic/chromosomal cause. These 173 cases were excluded from this study, leaving 1487 cases of intellectual disability with no identified genetic origin, referred to as intellectual disability in this paper (Table II).
Table II. Proportion of intellectual disability per 1000 live births between 1983 and 2001, by maternal alcohol exposure and Aboriginal status
|Intellectual disability severity||Non-aboriginal (n=41 320, 63.7%)||Aboriginal (n= 23 522, 36.3%)|
|Any alcohol-related diagnosis (n=10 576)||Comparison (n=30 744)||Net excessb||Any alcohol-related diagnosis (n=7760)||Comparison (n=15 762)||Net excessb|
| n ||Proportion (%)a (95% CI)|| n ||Proportion (%)a (95% CI)|| n ||Proportion (%)a (95% CI)|| n ||Proportion (%)a (95% CI)|
|All intellectual disabilitiesc||265||25.1 (22.2–28.2)||411||13.4 (12.1–14.7)||11.7 (8.6–15.1)||358||46.1 (41.7–51.0)||453||28.7 (26.2–31.5)||17.4 (12.2–22.9)|
|Mild–moderate||247||23.4 (20.6–26.4)||383||12.5 (11.3–13.8)||10.9 (7.9–14.2)||346||44.6 (40.2–49.4)||420||26.6 (24.2–29.3)||18.0 (12.8–23.3)|
|Severe||17||1.6 (1.0–2.6)||26||0.8 (0.6–1.2)||0.8 (0.0–1.8)||11||1.4 (0.8–2.5)||33||2.1 (1.5–2.9)||–0.7 (–1.7 to 0.6)|
The proportion of intellectual disability in all exposed non-Aboriginal children was 25.1 per 1000 live births (95% CI 22.2–28.2) and 13.4 per 1000 (95% CI 12.1–14.7) for the comparison children, with a net excess proportion of 11.7 per 1000 live births (Table II). For Aboriginal children, the proportion was 46.1 per 1000 live births (95% CI 41.7–51.0) in the exposed cohort and 28.7 per 1000 live births (95% CI 26.2–31.5) in the comparison cohort, giving a net excess proportion of 17.4 per 1000 live births. In the majority of cases, the intellectual disability was classified as mild–moderate. The net excess proportion of severe intellectual disability in exposed children was 0.8 per 1000 live births (95% CI 0.0–1.8) for non-Aboriginal children and −0.7 per 1000 live births (95% CI −1.7 to 0.6) for Aboriginal children, with the proportion of severe intellectual disability in Aboriginal comparison children being more than twice that of the non-Aboriginal comparison children (2.1 vs 0.8; Table II).
There were 66 children (0.4% of exposed) with a diagnosis of FAS recorded on the Western Australia Register of Developmental Anomalies; eight (12%) were non-Aboriginal and 58 (88%) were Aboriginal (results not tabled). Approximately one-third (31.8%) of children with FAS had received a diagnosis of intellectual disability, giving a proportion of 318 cases of intellectual disability per 1000 children with FAS, of whom 90% had mild–moderate intellectual disability.
When a maternal alcohol-related diagnosis was recorded during pregnancy, the overall proportion of intellectual disability in non-Aboriginal children was 50.8 per 1000 live births (95% CI 29.9–84.9) with a net excess proportion of 37.4 per 1000 live births (Table III). A smaller increase in excess proportions was evident when a maternal diagnosis was recorded either pre or post pregnancy but not during pregnancy. The proportion of intellectual disability in the offspring of mothers with alcohol diagnoses recorded both pre and post pregnancy, but not during pregnancy, was 37.2 per 1000 live births (95% CI 25.5–54.0) with a net excess of 23.8 per 1000 live births.
Table III. Proportion of intellectual disability per 1000 live births between 1983 and 2001, by timing of maternal alcohol-related diagnosis and Aboriginal status
|Timing of exposure||Non-aboriginal (n = 10 576)||Aboriginal (n = 7760)|
| na (%)|| nb ||Proportion (%)c (95% CI)||Net excessd|| na (%)|| nb ||Proportion (%)c (95% CI)||Net excessd|
|During pregnancy||256 (2.4)||13||50.8 (29.9–84.9)||37.4 (16.5–71.6)||443 (5.7)||37||83.7 (61.3–113.3)||54.8 (32.3–84.4)|
|≤1y pre pregnancy||518 (4.9)||10||19.3 (10.5–35.2)||5.9 (3.0–21.8)||358 (4.6)||24||67.0 (45.5–97.8)||38.3 (16.5–69.2)|
|≤1y post pregnancy||280 (2.6)||6||21.4 (9.9–46.0)||8.0 (3.6–32.6)||310 (4.0)||18||58.1 (37.0–89.9)||29.4 (8.1–61.3)|
|>1y pre pregnancy||1770 (16.7)||53||29.9 (23.0–39.0)||16.6 (9.5–25.7)||779 (10.0)||41||52.6 (39.0–70.6)||23.9 (10.0–42.1)|
|>1y post pregnancy||7752 (73.3)||183||23.6 (20.5–27.2)||10.2 (6.8–14.1)||5843 (75.3)||238||40.7 (36.0–46.1)||12.0 (6.5–17.9)|
|Pre and post pregnancy (not during pregnancy)||698 (6.6)||26||37.2 (25.5–54.0)||23.8 (12.1–40.7)||930 (12.0)||59||63.4 (49.5–81.0)||34.7 (20.5–52.4)|
For Aboriginal children, the overall proportion of intellectual disability was 83.7 per 1000 live births (95% CI 61.3–113.3) for an alcohol-related diagnosis recorded during pregnancy, giving a net excess proportion of 54.8 per 1000 live births (Table III). The excess proportions for each of the other categories without an alcohol-related diagnosis recorded during pregnancy were higher than for non-Aboriginal offspring, ranging from 12.0 per 1000 live births when an alcohol-related diagnosis was recorded more than 1 year post pregnancy to 38.3 per 1000 live births when an alcohol-related diagnosis was recorded within 1 year pre pregnancy. The proportion of intellectual disability in the offspring of mothers with alcohol diagnoses recorded both pre and post pregnancy, but not during pregnancy, was 63.4 per 1000 live births (95% CI 49.5–81.0), with a net excess of 34.7 per 1000 live births (Table III).
Non-Aboriginal children of mothers with any alcohol-related diagnosis had increased odds of intellectual disability compared with comparison children (adjusted OR [aOR] 1.44; 95% CI 1.18–1.75; Table IV). Increased odds were found when an alcohol-related diagnosis was recorded during pregnancy (aOR 2.89; 95% CI 1.62–5.18) and when diagnoses were recorded more than 1 year pre pregnancy (aOR1.87; 95% CI 1.36–2.57). When alcohol diagnoses were recorded both pre and post pregnancy, but not during pregnancy, the odds ratios doubled (aOR 1.95; 95% CI 1.25–3.05). These results remained valid after removing children with FAS from the analyses (Table IV).
Table IV. Odds ratios for intellectual disability by maternal alcohol-related diagnosis and Aboriginal status (for live births between 1983 and 2001)
| ||Non-aboriginal||Non-aboriginal, no FASc, ORb (95% CI)||Aboriginal, ORa (95% CI)||Aboriginal, no FASc, ORa (95% CI)|
|ORa (95% CI)||ORb (95% CI)|
|Any alcohol diagnosis|
| No||1.00||1.00||1.00||1.00|| |
| Yes||1.81 (1.53–2.14)||1.44 (1.18–1.75)||1.43 (1.17–1.74)||1.66 (1.42–1.96)||1.58 (1.34–1.86)|
|Timing of alcohol diagnosis|
| No alcohol diagnosis||1.00||1.00||1.00||1.00||1.00|
| During pregnancy||3.52 (1.96–6.34)||2.89 (1.62–5.18)||2.71 (1.48–4.98)||3.12 (2.13–4.56)||2.71 (1.81–4.07)|
| ≤1y pre pregnancy||1.15 (0.60–2.20)||0.90 (0.47–1.73)||0.90 (0.47–1.73)||2.30 (1.49–3.55)||2.02 (1.28–3.19)|
| ≤1y post pregnancy||1.52 (0.70–3.30)||1.17 (0.54–2.53)||1.17 (0.54–2.52)||1.95 (1.19–3.20)||1.75 (1.04–2.94)|
| >1y pre pregnancy||2.27 (1.67–3.09)||1.87 (1.36–2.57)||1.86 (1.35–2.56)||2.23 (1.56–3.19)||2.20 (1.54–3.16)|
| >1y post pregnancy||1.71 (1.41–2.07)||1.33 (1.07–1.66)||1.32 (1.06–1.65)||1.44 (1.20–1.73)||1.39 (1.16–1.67)|
| Pre and post pregnancy (not during pregnancy)||2.71 (1.76–4.16)||1.95 (1.25–3.05)||1.95 (1.25–3.05)||2.22 (1.62–3.02)||1.97 (1.42–2.75)|
The relationship between a maternal alcohol-related diagnosis and intellectual disability was more striking in Aboriginal children than in non-Aboriginal children (Table IV). The aOR for intellectual disability in Aboriginal children of mothers with any alcohol-related diagnosis was 1.66 (95% CI 1.42–1.96), and increased odds ratios were observed for each of the six time periods. The odds ratio was increased three-fold when a diagnosis was recorded during pregnancy (aOR 3.12; 95% CI 2.13–4.56), and doubled when an alcohol-related diagnosis was recorded not during pregnancy but up to 1 year before pregnancy or more than 1 year prior to pregnancy, or when alcohol diagnoses were recorded both pre and post pregnancy. As with the non-Aboriginal analyses, the results remained valid following removal of children with FAS (Table IV).
The population-attributable fraction of intellectual disability when a maternal diagnosis occurred during pregnancy was 0.14% (95% CI 0.02–0.29%) for non-Aboriginal children and 2.8% (95% CI 1.09–4.68%) for Aboriginal children (results not shown). The population-attributable fraction for any alcohol-related diagnosis was 1.3% (95% CI 0.81–1.86%) for non-Aboriginal and 15.6% (95% CI 10.85–20.94%) for Aboriginal children. When combined, the population-attributable fraction equates to 3.8% (95% CI 2.84–4.89) of all cases of intellectual disability in Western Australia.
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- What this paper adds
- Supporting Information
These results provide the first population-based evidence that a maternal alcohol-related diagnosis, which can be considered a proxy for maternal alcohol use disorder, is the leading known cause of intellectual disability with no identified genetic origin. In total, 3.8% (95% CI 2.84–4.89%) of all cases of intellectual disability in Western Australia were associated with maternal alcohol use disorder. Furthermore, 1.3% (95% CI 0.81–1.86%) of intellectual disability in non-Aboriginal children and 15.6% (95% CI 10.85–20.94) in Aboriginal children of mothers with an alcohol-related diagnosis could potentially be prevented by eliminating heavy alcohol use by these mothers during pregnancy.
The net excess proportion of intellectual disability provides an estimate of the proportion of intellectual disability occurring in the children of mothers with an alcohol-related diagnosis. Among the pregnancies during which an alcohol-related diagnosis was recorded in the mother, 3.7% (95% CI 1.65–7.16%) of the children of non-Aboriginal mothers and 5.5% (95% CI 3.23–8.44%) of children of Aboriginal mothers had an intellectual disability. This is the first study to provide health professionals with evidence on which to base their clinical advice on the risk of intellectual disability in the children of women drinking heavily in pregnancy.
Calculation of the population-attributable fraction requires a large population-based study, and few studies investigating risk factors for intellectual disability have this capacity. We are not aware of any other behavioural risk factor for intellectual disability that has an attributable fraction greater than the 3.8% reported for the children of mothers with an alcohol-related diagnosis, and in particular the attributable fraction of 15.6% for Aboriginal children. We recognize that these are conservative estimates. Cases of intellectual disability on the IDEA database can be ascertained up to 18 years of age, with 80% identified by 10 years of age.17 Twenty per cent of the cohort in this study was between 6 and 9 years of age at the end of follow-up in 2007, so some cases of intellectual disability would not have been identified. Also, as these results relate to the children of mothers with an alcohol use disorder that has been identified in the health setting, they represent the extreme end of the exposure continuum.
As the risk of intellectual disability was the same for exposed non-Aboriginal and Aboriginal cohorts, the population-attributable fraction will be influenced by the prevalence of the exposure in these communities. The reported prevalence of alcohol use disorders in non-Aboriginal Australian women is 3%29 to 5.0%,30 higher than the 2.3% obtained in this study (unpublished data), which would generate a higher population-attributable fraction for intellectual disability than the estimate of 1.3% obtained in this study. We are unaware of any estimates of the prevalence of alcohol use disorders for Aboriginal mothers. However, it is possible that underascertainment of Aboriginal mothers with an alcohol-use disorder also occurred with this study design. Alcohol-related problems are more common in rural/remote regions than in metropolitan regions in Australia;31 the majority of Aboriginal mothers in this study lived in rural or remote regions, and we were unable to access service data for Aboriginal-specific health services and rural drug and alcohol services for this study. It is also possible that Aboriginal mothers are more open about their drinking, making it easier for health professionals to identify, or that health professionals are more likely to record an alcohol diagnosis for Aboriginal than for non-Aboriginal mothers; however, we are unable to examine these issues in this study.
A measure of the under-recognition of alcohol use disorders during pregnancy is the lower attributable fraction obtained for intellectual disability when a maternal alcohol-related diagnosis was recorded during pregnancy. The estimates of 0.14% for non-Aboriginal children and 2.8% for Aboriginal children when a maternal alcohol-related diagnosis was recorded during pregnancy are considerably less than the 1.3% and 15.6% respectively, obtained for an alcohol-related diagnosis recorded at any time of a woman’s life. Health professionals have a key role to play in identifying heavy alcohol consumption in women of childbearing age and pregnant women and implementing brief interventions to reduce the risk of alcohol-exposed pregnancies.32 These are essential for preventing alcohol-related intellectual disability.
The risk of intellectual disability in children of mothers with an alcohol-related diagnosis transcends race. We acknowledge that for some Aboriginal children, particularly those in remote regions, assessments of intellectual disability may be culturally inappropriate, putting these children at a disadvantage. However, psychologists in Western Australia are generally aware of the need to use ‘culture-free’ tools for Aboriginal children.33 In both non-Aboriginal and Aboriginal children, the odds of intellectual disability were increased three-fold when an alcohol-related diagnosis was recorded for the mother during pregnancy, and this increase remained after adjusting for potential confounding factors and following removal of cases of FAS. The prevalence of FAS in Western Australia (0.5/1000 births)24 is lower than many published estimates (2–7/1000).9 There is a lack of recognition of FAS in Western Australia11 and limited diagnostic capacity so it is probable that other exposed children with intellectual disability in this cohort have undiagnosed FAS. However, it is likely that some of the exposed children with intellectual disability will lack the classic FAS facial features and therefore fit the diagnostic criteria for an ARND. So, given that FAS is less common than maternal alcohol use disorder,9,29,30 not all children with FAS have intellectual disability, and that many children with alcohol-related intellectual disability may be more appropriately classified as having an ARND, it is more appropriate to state that maternal alcohol use disorder is the leading known non-genetic cause of intellectual disability, rather than FAS, as suggested by Abel and Sokol 30 years ago.1,2
Linkage of routinely collected population-based data is a valid means of identifying cases admitted to hospital for a health-related condition34 and minimizes loss to follow-up of high-risk mothers and their children,13,35 thereby overcoming many of the difficulties inherent in epidemiological studies investigating maternal alcohol consumption during pregnancy and intellectual disability.16,19 However, the majority of alcohol diagnoses were for acute intoxication and we could not examine the exact timing of exposure and whether there were extended periods of sobriety which could have reduced risk to the fetus. Overall, the proportion of intellectual disability in the non-Aboriginal comparison cohort (13.4/1000) was similar to the published Western Australian prevalence,17 and the proportion of intellectual disability in children with FAS (318/1000 children with FAS) was consistent with published estimates.7 This consistency supports the validity of the data.