Study eligibility criteria

In line with our study protocol, studies were included if they were case control or cohort studies published any time before 1 March 2012, in the English language in a peer reviewed journal. Studies which reported data on low or moderate alcohol exposure (defined as an average of less than 10 grams per day or 70 grams per week during pregnancy) compared to not drinking during pregnancy were included. Studies which reported on any measure or component of language, speech and communication delay, development or disorder in children up to 18 years were included, for example, acquired language disorders and semantic pragmatic disorders (see Additional file 1). We excluded duplicate publications and studies published only as abstracts. Other cognitive and developmental outcomes and nonverbal language outcomes were excluded. Studies of populations with special developmental needs, such as autism spectrum disorder, were also excluded. This review was not registered with PROSPERO [28].

Search strategy

Embase, PubMed, Cinahl, SCOPUS, Web of Knowledge and The Cochrane Library were searched from their inception up until 1 March 2012 using all appropriate MESH headings related to “alcohol”, “speech and language outcomes”, “pregnancy” and “risk or odds” (see Additional file 1 for detailed search strategy: note that search strategy was not peer reviewed). Search limits of “human” and “female” were applied in PubMed only. All associated MESH terms were combined using “OR”. Finally, all terms were combined using “AND” to yield a total number of abstracts for each database. Reference lists of retrieved articles were also hand searched for further potentially relevant articles. Additionally, the authors of the cohort study by Faden and Graubard [29] were contacted for additional information on their study which was not available in the published paper. All citations were imported to Endnote citation manager and duplicates removed. Figure 1 shows a flow diagram of the results of the search strategy implemented.

Study and data collection processes

Quality assessment

Search results

Overall, 1,397 abstracts were identified of which 387 duplicates were removed (Figure 1). Of the 1,010 articles remaining, 45 full text articles were retrieved. A further six citations were identified through hand searching of full texts leading to a total of 51 studies to undergo full review. Both assessors (LMOK, PMK) independently reviewed all 51 full texts in accordance with inclusion and exclusion criteria and disagreements were settled by consensus. The main reasons for exclusion were lack of reporting on the exposure and outcome of interest and exclusion due to study of alcohol in populations with other developmental disorders such as autism spectrum disorder. Three cohort studies were included, totaling 10,642 women. A summary of the study characteristics and results is shown in Tables 1 and 2.

Description of included studies

Two studies were from the United States and one study was from Australia. One study collected data on alcohol exposure during pregnancy through direct face to face interviews [31] while the remaining two studies collected exposure status after pregnancy through a postal survey [29, 30]. O’Leary et al. [30] collected data on dose, pattern and timing of exposure for the three months before pregnancy and each trimester separately approximately 12 weeks after delivery. Faden and Graubard [29] collected data on mean alcohol drinks per day during pregnancy through a postal survey after pregnancy, while Greene et al. [31] collected data on the average number of ounces of alcohol per day reported to have been consumed over all sampled days throughout pregnancy by a face to face interview during pregnancy. All three studies used different validated instruments to measure language delay including the parent reported Ages and Stages Questionnaire [30], a parent reported seven-item Language Scale from the Denver Developmental Scale [29] and the Sequenced Inventory of Communication Development (SICD) at one, two and three years [31], a standardized procedure directly administered in the home of the child to diagnose developmental delay in the acquisition and use of language. Only two of the three studies (O’Leary et al. [30] and Greene et al. [31]) controlled for relevant confounders in their analyses and effect measures were also significantly heterogeneous. O’Leary et al. [30] reported crude and adjusted odds ratios while estimates by Faden and Graubard [29] reported mean number of drinks per day for each level of the seven-item Language Scale used. Greene et al. [31] reported mean SICD measures for selected levels of absolute alcohol per day at one, two and three years for expressive and receptive language outcomes.

Systematic review results

Table 3 describes the results of included studies. O’Leary et al. [30], retrospective cohort in 1,759 largely married, educated and non-indigenous Australian women, defined low alcohol consumption during pregnancy as 20 g or less per occasion or less than weekly. For low drinking in the first trimester, the odds of language delay were 0.97 (95% confidence interval (CI) 0.65 to 1.43) indicating that low drinkers were 3% less likely to have children with language delay compared to abstinent mothers though the results were not statistically significant as indicated by the wide confidence intervals that span the null value (odds ratio of 1). For low drinking in the second trimester the odds of language delay were 0.87 (95% CI 0.59 to 1.28) and for the third trimester, 0.84 (95% CI 0.57 to 1.23) which also indicated slightly reduced odds of language delay in low drinkers (13% and 16%, respectively) that were not statistically significant as indicated by the confidence intervals spanning the null value. Estimates were adjusted for a range of confounders, including maternal age, parity, marital status, smoking for each trimester, illicit drug use, depression, anxiety and stress, family factors (antenatal income, presence of partner in household, parenting ability, family functioning).

Faden and Graubard [29] retrospective cohort study of 8,885 women reported to have been sampled representatively from the national birth certificate in the United States but did not report socio-demographic and health characteristics of participants. The response rate upon first recruitment to the study was 74% with 83% of the original cohort completing the three-year follow-up. Stratified sampling by both ethnicity and birth weight was conducted. A seven-item language scale was used to measure language development. Potential scores on the scale ranged from 1 to 7 with a lower score indicating lower levels of language development. Mean alcoholic drinks per day during pregnancy were reported for each level of the seven-item language scale. Covariates were not adjusted for and the results reported did not show any dose–response relationship between lower levels of language development and mean number of drinks per day.

The prospective cohort study of 359 mother-infant pairs by Greene et al. 1990 [31] in women attending a hospital for antenatal care comprised over 50% black with a mean age of 22 and with over 30% reporting use of marijuana during pregnancy. Women who delivered small for gestational age infants or whose infants were admitted to neonatal intensive care were excluded from the study. This group was also socio-economically disadvantaged. The results were reported in mean SICD measures for selected levels of absolute alcohol per day and were adjusted for sex, race, parental education, maternal age, reported usage of street drugs, the day of first antenatal visit, the Home Observation for the Measurement of the Environment (HOME) score, the precise age at testing, the ratings of psychosocial stress, medical problems and maternal IQ. Significant differences in expressive and receptive language development at one, two and three years were not evident for all three measures of alcohol use obtained, including abstinence, one-third of a UK standard drink per day, greater than one-third to one and a half UK standard drinks per day or approximately two UK standard drinks per day.

Quality assessment

The results of the quality assessment undertaken are shown in Table 3. Attrition bias was present in all three studies and may have significantly impacted results. In addition, selection, confounding and analytic bias were also present. In the study by Greene et al. 1990 [31], selection bias was deemed to be ‘moderate’ due to ambiguous sample selection but ‘minimal’ in both other studies. Confounding bias was deemed to be ‘high’ in Faden and Graubard [29] due to lack of control for confounders but ‘minimal’ in both other studies while analytic bias, though present in both Faden and Graubard [29] and Greene et al. [31], was relatively low.

Implications for practice

MRI studies have shown that prenatal alcohol exposure can impact upon a number of regions of the brain involved in verbal communication development, such as the corpus collosum, by displacing it, producing shape variability or reducing volume, area and length [22]. Though a lack of association between moderate alcohol use during pregnancy and speech and language development in infants is not implausible, given the low number of studies conducted, the inherent problems of accurate alcohol measurement during pregnancy and lack of biological plausibility with pathophysiological evidence, further research is required. In particular, future studies which more robustly assess the impact of alcohol use on speech and language outcomes due to the likely impact of attrition, selection and confounding biases are required. Losses to follow-up were considerable threats to validity in studies reviewed. Efforts to account for both participation bias which occurs upon recruitment to studies and attrition bias occurring later in the study should be incorporated in future studies of this nature. The complex nature of the development of speech and language delays including the interaction of environmental, neurodevelopmental and familial factors [5] as well as the underlying cultural and ethnic differences that may result in varying attitudes, practices and norms relating to alcohol and speech and language outcomes must be addressed [16]. Consequently, until, large scale, population-based, longitudinal studies of gestational alcohol use and speech and language outcomes emerge, healthcare providers should advise women to abstain from consuming alcohol during pregnancy while policy makers should remain aware of limited research evidencing safe alcohol consumption thresholds during pregnancy.