To determine what is known about the effects of prenatal alcohol exposure, corresponding to low-to-moderate levels of maternal consumption, on pregnancy outcomes. These include pregnancy complications, delivery outcomes and Fetal Alcohol Syndrome (FAS) features. This will include the assessment of systematic reviews and meta-analyses. A particular focus will be placed on identifying practical and meaningful outcomes of alcohol toxicity during pregnancy.
Publications will be identified by searching the following major relevant databases: Medline, Embase, web of science and Psychinfo. All databases will be searched from inception. Internet searches will be carried out using Google Scholar. Attempts to identify further studies will be made by examining the reference lists of included studies and of previous reviews. All studies to be restricted to those published in the English language only.
Types of study to be included
1) Prospective studies and systematic reviews/meta-analyses of prospective studies (cohort or case-control studies nested in a cohort). 2) Natural experiments / studies using instrumental variables to improve casual inference, including Mendelian Randomization (MR) studies 3) Sibling comparison studies 4) Parental comparisons
Condition or domain being studied
Pregnancy and delivery outcomes as well as offspring outcomes (from the domains affected by Fetal Alcohol Syndrome (FAS))
Pregnant women or women who are trying to become pregnant sampled from the general population. Cohorts of pregnant women with alcohol abuse/dependency will be excluded.
Inclusion: low–to-moderate levels of prenatal alcohol consumption (up to 10.4 UK units or 83 g/week).
Exclusion: studies will be excluded if there was no quantitative measure of alcohol consumption that could be converted to UK standard units or grams of alcohol and if there was insufficient data for an (adjusted and/or crude) effect measure of low–moderate consumption to be extracted. Cohorts of pregnant women with alcohol abuse/dependency will be excluded.
women with no or very sporadic alcohol consumption in pregnancy.
Outcomes: (in both children and adults)
1) Pregnancy complications
- Intra uterine growth restrictions (IUGR)
- Premature labour and birth- Gestational age
- Preeclampsia and gestational hypertension
- Low amniotic fluid (oligohydramnios)
- Gestational diabetes
- Placenta previa
2) Delivery outcomes
- Birth weight/ low birth weight/ small for gestational age (SGA)
- Growth restrictions (height- measurements of growth restriction)
- Cranium size/ head circumference
- Developmental delays
- Behaviour complications
- Cognitive impairment / IQ
- Attention scores / Attention deficit and hyperactivity disorder (ADHD)
Data extraction, (selection and coding)
Selection of studies:
Titles and abstracts will be screened independently by one reviewer (a random selection of 20% will also be screened by a second reviewer independently) with inclusion/exclusion being decided according to prespecified criteria. Discrepancies will be discussed and disagreements resolved through consensus. The full-text of each of the articles identified through screening of titles and abstracts will be obtained in order to determine their inclusion in the review.
Data extraction will be carried out using Microsoft Access. This will be piloted on a small selection of studies and adjusted as necessary. Relevant data will be documented from each identified study including information on study design and location, population characteristics, exposures studied (including timing of exposure), methods used to ascertain exposures, outcomes studied, method of outcome ascertainment (including person reporting the outcome, whether parent, teacher, health professional, researcher, child…), study results (from both unadjusted and fully adjusted regressions), statistical adjustments etc. Data extraction will be carried out independently by one reviewer and a random selection of 20% will checked by a second reviewer. Discrepancies will be resolved through discussion or referral to a third reviewer. Where necessary, authors will be contacted for additional information.
Risk of bias (quality) assessment
Studies that did not adjust for smoking and maternal education/social class as potential confounders in their final model will be considered to be of low evidence quality.
Strategy for data synthesis
The impact of low-to-moderate alcohol use on pregnancy and related outcomes will be investigated using high-low methods of meta-analysis techniques; however, due to anticipated low number of studies for some outcomes, a formal meta-analysis may not be appropriate for some of the outcomes. Where meta-analysis is not possible, a narrative summary of findings will be carried out. Random-effect meta-analysis will be performed alongside fixed-effect in the presence of high levels of between-studies heterogeneity (measured through I2). Item response theory (IRT) will be used to combining results from different scales if required. The likelihood of small study bias deriving from publication bias will further be assessed through drawing funnel plots.
Analysis of subgroups or subsets
Where the included number of studies in the meta-analysis is large enough, sub-group analyses will be performed for 1) studies adjusting for smoking and maternal education/social class; 2) studies reporting separately on the effects of alcohol use in different gestational periods; 3) studies using different exposure/outcome assessments.
We anticipate dissemination to regional and national public health directors
Contact details for further information
MRC Integrative Epidemiology Unit
School of Social and Community Medicine
University of Bristol
Bristol BS8 2BN
Organisational affiliation of the review
Dr Loubaba Mamluk, University of Bristol, UK Dr Luisa Zuccolo, University of Bristol, UK Ms Theresa Moore, University of Bristol, UK Ms Alison Richards, University of Bristol, UK
Dr Luisa Zuccolo, University of Bristol, UK Dr Sarah Lewis, University of Bristol, UK Dr Abi Fraser, University of Bristol, UK Professor Jenny Donovan, University of Bristol, UK Professor George Davey Smith, University of Bristol, UK
Anticipated or actual start date
12 January 2015
Anticipated completion date
01 September 2015
National Institute of Health Research, Medical Research Council, University of Bristol. UK
Formal screening of search results against eligibility criteria
Risk of bias (quality) assessment
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.