ALCOHOL DURING PREGNANCY – IS THERE A SAFE LIMIT?

HOMEPAGE

The aims of this literature review are to evaluate evidence on the effects of drinking during pregnancy on the foetus and subsequently determine what the guidelines should state as the safe limit of alcohol consumption during pregnancy.

The objectives are:1.To determine the effects of varying quantity of alcohol consumption at different stages of pregnancy.2. To determine the consequences of binge drinking (more than 7.5 units in a short period of time)1 on the unborn child.3. To compare the short and long term effects of maternal alcohol consumption during pregnancy on the child after birth.4. To determine the predictors of antenatal alcohol use in pregnant women and to consider the relationship between pre-pregnancy alcohol consumption and continued drinking during pregnancy.5. To compare the current guidelines to the conclusions we draw from our literature review.

This site was made by a group of University of Edinburgh medical students who studied this subject over 10 weeks as part of the SSC: SSC2a Study Guide.

This website has not been peer reviewed.

We certify that this website is our own work and that we have authorisation to use all the content (e.g. figures / images) used in this website.

Our tutor Dr Sunit Rane guided us through this project and provided knowledge and support throughout.

INTRODUCTION

There is conflicting evidence on the safe limit of alcohol consumption during pregnancy, and through doing this literature review, we aim to draw a conclusion based on the current evidence available. The prevalence of alcohol consumption throughout pregnancy is widely underreported2, but it is estimated around 30% of pregnant women continue to drink, with 8% of pregnant women binge drinking during pregnancy3. In the United Kingdom it is estimated that 16% of child bearing age women have an alcohol related disorder and consumption of alcohol both pre-pregnancy and during pregnancy is known to be detrimental to the unborn foetus2. Foetal alcohol spectrum disorder (FASD) is the umbrella term for a wide range of pathological characteristics, both physical and neurological, caused by maternal alcohol consumption during pregnancy and it is the leading cause of non-genetic intellectual disability in the western world.4 It is also fully preventable and could, in theory, be eliminated from society. However there is little information relating to the number of sufferers due to misdiagnosis and under-representation of pregnant women admitting they drink alcohol during pregnancy. The number of cases of foetal alcohol syndrome (FAS) – the most severe form of FASD - in the United Kingdom is thought to be 0.21 per 1000 live births5.

This literature review serves to: analyse the effects of maternal alcohol consumption on the foetus; investigate the effect of binge-drinking throughout pregnancy; look at the long term effects of maternal alcohol consumption on the child; discuss the factors contributing to maternal alcohol consumption; and give our recommendations for government guideline amendments.

EFFECT OF ALCOHOL ON THE FOETUS

A level of ambiguity permeates the multiple guidelines on maternal alcohol consumption prior to and during pregnancy. Evidence from several studies demonstrated that pregnant woman should be universally informed to completely refrain from alcohol consumption throughout the whole gestational period. The study by Feldman et al. demonstrated how the six clinical features of FASD (smooth philtrum; thin vermillion border; short palpebral fissures; microcephaly; and growth deficiencies in weight and height) are dose related without evidence of a threshold6. Results from this study indicated that even one drink per day on average increases the risk of five of six clinical features of FASD suggesting that the government guidelines should be re-evaluated. Therefore it would appear feasible to conclude that any level of alcohol consumption has a detrimental effect on foetal development. The 992 woman in this study were self-referred and anonymised to minimise selection bias and underreporting due to the fear of stigmatisation. A blinded dysmorphologist performed the examination expelling confirmation bias. Moreover, with regards to gestational timing of alcohol consumption, the foetus was found to be most susceptible in the first trimester6.

Emphatically this result was paralleled in the study conducted by Nykjaer et al. which revealed that, “Even women adhering to the guidelines in the first trimester were at significantly higher risk of having babies with lower birth weight, lower birth percentile, and preterm birth compared to non-drinkers, after adjusting for confounders (P<0.05)7. This study was conducted using questionnaires in different trimesters and a midwifery interview. This method minimises recall bias and the personalised interview process increased the likelihood of accurate reporting. However the reduced response rate in the third trimester (<40%) and the relatively small cohort size means caution must be taking when considering how applicable the findings are to the total population7.

In contrast to the above findings, a retrospective postal survey conducted by O’Leary et al. found that there was little difference between the outcomes of mothers who abstained and those with low alcohol consumption2. This was with particular regard to preterm births and poor foetal growth. The study found a trend between the risk of preterm birth and increasing levels of alcohol exposure, although this finding lacked statistical significance; after the results were adjusted for smoking, the correlation was eliminated. The inconclusive nature of these results could be due to a relatively small sample size (4719) or the retrospective nature of the data collected. Postal surveys were sent out to mothers 12 weeks postpartum which may have led to noteworthy underreporting and recall bias; therefore decreasing the validity of the results2.

Although some research did not find a link between low to moderate alcohol consumption and foetal alcohol syndrome, the majority of acclaimed and acknowledged research does demonstrate a clear link. From this, we deduced that abstaining from alcohol is a vital component in the physiological development of a healthy foetus.

BINGE DRINKING

There is conflicting evidence that drinking occasionally throughout pregnancy causes foetal harm,8,9. However, binge drinking is known to cause significant short and long-term consequences10. For women, binge drinking is defined as consuming six or more units in one sitting and studies have found that as many as 1 in 50 women binge drink whilst pregnant11. There is plenty of evidence to suggest that binge drinking and heavy drinking throughout pregnancy have significant detrimental impacts on foetal development. A study in Australia by Srikartika and O’leary compared the outcomes of babies born to

mothers with an alcohol related diagnosis, and those without. It categorised the mothers further into Aboriginal and Non-Aboriginal categories due to the significant lifestyle differences between them11. Results showed that mothers with an alcohol-related diagnosis before and/or during pregnancy were at a 2-2.5-fold increased risk of having a preterm birth. There was also a direct correlation between heavy drinking and the prevalence of offspring born small for gestational age (SGA) and with a low Apgar score (a common measurement for all neonates to determine health). The large sample size of 84,364 women allowed for detailed comparisons and statistically significant results as the sample was representative of the total population. The cases (mothers) were selected on the basis of having an alcohol-related diagnosis (international classification of disease 9/10), that was registered on the Western Australia Data Linkage System, giving a total of 23,573 participants in this group. The control group was selected on the basis of not having an alcohol-related diagnosis and being registered on the Midwives Notification System (MNS), giving a total of 60,791 participants. These mothers were then matched to the mothers in the case group to minimise the influence of confounding factors and to increase the comparability between groups11. This method allowed for many women to be included in the study, whilst excluding the possibility of bias from the data-collection stage. However there is the potential that some episodic patterns of binge drinking may not have been detected by health services and therefore participants suitable for the case group could have been misclassified into the control group, leading to an error in the results.

Another study by O’Leary et al., which used similar methods to investigate the correlation between maternal alcohol use before, during and after pregnancy and the occurrence of Sudden Infant death Syndrome (SIDS) and infant mortality excluding SIDS further indicated these results12. This study also classified the case group of 21,841 as offspring born from mothers with evidence of an alcohol-related diagnosis. The control group of 56,054 offspring were born from non-alcoholic mothers who were again frequency matched from the MNS. This study found that offspring exposed to heavy alcohol consumption at any point before, during or after pregnancy were seven times more likely to die of SIDS and twice as likely to die of infant death not classified as SIDS. From these results it was found that 40% of these deaths could be directly linked to alcohol exposure while the other 60% were linked more closely to more environmental factors such as smoke inhalation, dehydration, viral infection and neglect. While this study had similar positives as the aforementioned, it is worth emphasising that this study also questioned whether mothers from the control group may have been misclassified at some stage of this study. Whilst these studies agreed with many others that there is a correlation between heavy maternal drinking and the risk of SGA, they did not assess the effect of low-level alcohol consumption. It also contradicted other studies that suggest alcohol is prevalent in lower socioeconomic groups and in those with poor access to antenatal care12.

In stark contrast to the papers already discussed, the study conducted by McCarthy et al. somewhat controversially concluded that binge drinking in the initial stages of pregnancy did not affect foetal development13. At 15 weeks of gestation participants were interviewed about their alcohol consumption pre and post pregnancy and the birth outcomes (SGA, reduced birth weight, pre-eclampsia and spontaneous preterm birth) were taken from medical records postpartum. Whilst this study had a moderate sample of 5,628, the significance of this was undermined by a number of factors. Women who were deemed to be at a higher risk of adverse pregnancy outcomes were excluded from the study, leading to selection bias. The retrospective nature of the study and the lack of anonymity naturally also introduced an element of recall bias13. Furthermore the lack of blinding of the midwives involved in the study considerably increased the likelihood of confirmation bias. Therefore from these limitations, it is reasonable to infer that until this study has been repeated, and the results replicated, the ideas presented should not be taken into account when reviewing guidelines.

LONG TERM EFFECTS OF MATERNAL ALCOHOL CONSUMPTION

The consequences for infants born to mothers who consume alcohol are significant in the short term as they are more likely to be premature, have a lower Apgar score at 5 minutes and be smaller for gestational age14. There are also long term effects with babies being diagnosed with foetal alcohol spectrum disorder (FASD) – long-term issues with mental health, intellectual ability and physical deformities2. These effects can be seen at various stages of life and can be measured in many different ways, including differences in facial features, growth, brain structure, cognitive function and behaviour. Some of these are easier to objectively measure than others and so give more reliable results. However, other measurements and findings must still be taken into account due to the lack of objective measurements of ‘normal’ behaviour and intelligence.

A study conducted by Skogerbǿ et al. examined the effects of low to moderate alcohol consumption and binge drinking in early pregnancy on executive function in 5 year old children15. The study did not find any noteworthy effects of low to moderate alcohol consumption during pregnancy, as all statistically significant results were disregarded after adjustment for confounding factors. However for children of mothers who drank heavily or engaged in binge drinking during pregnancy, there was a statistically significant decrease in cognitive ability and executive function. It should be noted that a possible limitation of this study is that although a lot of the executive functional development occurs between the ages of 2 and 5, adult level abilities are not developed until the completion of adolescence. To fully appreciate the impact of maternal alcohol consumption on executive function, more research needs to be carried out observing changes in both young children and adolescents. The case groups were sampled based on their mothers’ alcohol consumption throughout the pregnancy which was assessed at the first antenatal visit. When the children turned 5 years old, parents and teachers were given BRIEF score forms to complete. This was to assess the children’s higher executive function15. Although the BRIEF score is considered to be a highly reliable instrument, there may be bias amongst the recording of teachers’ and parents’ results. It should be noted that although these results were not statistically significant, this paper acknowledges that alcohol is a known teratogen and advised abstinence throughout pregnancy.

An investigation by Rousssotte et al. observed brain volumes using structural Magnetic Resonance Imaging (MRI) of 99 children, 56 of which had been exposed to prenatal alcohol consumption, with some suffering from FASD16. The subjects were aged between eight and sixteen and lived in a variety of geographical locations (Los Angeles, Cape Town and San Diego). After correcting for confounding factors, including scan location, age, and total brain volume, an extremely significant volume reduction was found for the case group in the diencephalon and basal ganglia. A direct correlation was found between the extent of the facial dysmorphology of the case group and the reduction in particular subcortical structures and IQ scores - a concept that the authors mentioned was corroborated by previous reports. It is fair to question whether effects of prenatal alcohol exposure were fully demonstrated as there may have been significant changes in brain structure as development progressed. However, the study’s statistical relevance was strengthened by a variety of measures taken. The study assessed all children exposed to alcohol regardless of whether they had been diagnosed with FASD or not. This is one of the pivotal features of the paper, illustrating that alcohol has a deleterious effect on foetal development even if FASD cannot be diagnosed. This is a significant finding and certainly highlights the need for adjustment of current government guidelines. Furthermore the geographical spectrum of the cohort makes the findings more relevant for global application. As stated above, confounding factors were accounted for, further increasing the credibility of the findings. For example, participants with significant physical or psychiatric disability were excluded16. Great regard should be placed on this report when assessing guidelines, as the findings are universally sound and indicative of the need for abstinence.

In addition, Eckstrand et al. are advocates of the findings of the above study. Their study investigated persistent dose-dependent changes in brain structure in 11 young adults with low to moderate alcohol exposure in utero17. Some interesting (if somewhat statistically questionable) results were reached. This paper used voxel-based morphometry and region-of-interest analyses to assess the volume of different areas of the brain and assess if prenatal alcohol exposure had any effect on these. It was concluded that, “grey matter loss was dose dependant with higher exposure producing more substantial losses”. Generally a small cohort size is associated with a proportional decline in statistical significance, introducing an element of selection bias. However in this particular study the adverse effects of confounding factors, and in particular socio-economic class, was efficaciously excluded17. This is compelling as different socio-economic standings could potentially introduce other issues such a maternal nutrition, education and access to health care during pregnancy. Therefore it could be reasoned that the small sample size’s effect on the significance of these findings is minimised by the removal of the confounding factors. Although the lack of blinding in the investigation could lead to confirmation bias, the objective, quantitative nature of the procedure makes this potential bias relatively insignificant as the technicians’ thoughts and stigmatisations of the mothers have no real impact on the outcome.

Moreover the investigation conducted by Callaghan et al. further explored the long term effects of alcohol exposure during pregnancy18. The study was a prospective longitudinal study that assessed the effects of low to moderate levels of maternal alcohol consumption on children’s intellectual ability, learning and attention at 14 years of age. Initially 7,223 participants were enrolled in the cohort study. At 14 years, 5,139 mothers and adolescents completed attention and learning questionnaires, and 3,731 (72.6%) adolescents attended the hospital to complete psychometric assessments. It was found that consumption at the level of less than 1 drink/day (0.5 oz. absolute alcohol) does not lead to adverse outcomes in relation to attention, learning and cognitive abilities. This opposes the findings of the investigation we analysed above which concluded that abstinence should be the universal advice given to pregnant mothers. This study takes into consideration many factors that could play a role in alcohol consumption in pregnancy including maternal age and education, marital status and total family income at 14 years, pre-pregnant maternal Body Mass Index (BMI) and level of maternal smoking in pregnancy. However despite this, the reliability of the report remains contentious due to a variety of flaws in this study, and thus this conclusion should be viewed with reservations. It must be considered that the catchment population of the hospital in terms of ethnicity and social class may differ to the societal average, and not represent the wider population. Mothers not included in this study were likely to be younger, less educated, financially more disadvantaged, and to have consumed more alcohol in early and late pregnancy. Binge drinking was also more likely than in included mothers. Given the low response rate in the high exposure category, a verdict cannot be reached on the effect of high alcohol consumption18. Therefore, it is possible to conclude that due to the selection bias throughout this report, its significance is minimal and the results should not be taken into consideration, unless the results are repeated in a more reliable study.

The study conducted by Robinson et al. demonstrated that light and moderate drinking in the first trimester of pregnancy was not found to directly impact childhood behaviour in a negative manner 19. After establishing maternal alcohol consumption during pregnancy, the Child Behavioural Checklist (CBCL) was used over 14 years to continually assess any abnormal behavioural changes in the child. The longitudinal nature of the study allowed for assessment throughout cognitive development of the children. While there was a sample size of 2,900, only 65% were followed up to the age of 14, and there was no mention of blinding throughout the study, which decreases the validity of the results19. The potential for recall bias and lack of consideration for heavy and binge drinkers, again impacts the significance of these findings, and therefore the results would need to be replicated to be of use when considering amending the guidelines.

FACTORS CONTRIBUTING TO MATERNAL ALCOHOL CONSUMPTION

It is known that women who drink before falling pregnant are more likely to continue3, therefore tailored support should be given to help reduce their alcohol consumption due to the detrimental effects it can cause. The predisposing factors that increase a women’s likelihood of drinking before and during pregnancy also need to be addressed, while reducing the occurrence of other factors that trigger drinking of alcohol in pregnancy such as smoking and poor diet20.

A study conducted by Anderson et al. indicated that pre-pregnancy alcohol consumption was one of the fundamental predictors of antenatal alcohol use20. The data was collected from the Australian Longitudinal Study on Women’s Health (ALSWH) to investigate the link between antenatal alcohol consumption and the environmental and social influences surrounding women who were pregnant over a ten year period. During the time of the study, there were inconsistencies in the recommendations given to pregnant women. Initially they recommended abstinence, however this advice was altered to regard low level drinking as acceptable. Critically when the guidelines suggested a low level of drinking was acceptable; women were 1.6 times more likely to consume alcohol than when the guidelines advocated abstinence. This marked increase resulted in the re-evaluation of the guidelines and the reversion back to 0 units. The study considered 36 variables that could potentially predict prenatal alcohol consumption. This notably included prenatal alcohol consumption, Health Care Card status, prior general health fertility problems and any drug use. Women with previous fertility problems were less likely to consume alcohol as they would have increased contact with health care professionals and increased awareness of any potential negative outcomes. Access to health care also influenced the likelihood of prenatal alcohol consumption as women with a Health Care Card were less likely to drink. There was a correlation between worse previous general health, smoking throughout pregnancy and illicit drug use with the continuation of alcohol use throughout pregnancy. By far the biggest correlation was with previous alcohol consumption as 82% of women in this category were classified as antenatal drinkers20. The 1,969 participants were selected from a single health insurance firm; therefore this study may not be fully representative of the population, leading to selection bias. Furthermore the study relies on self-reporting, naturally introducing the risk of under-reporting of harmful exposures and recall bias. Despite this, the measures taken by the authors of this paper to ensure statistically significant results maximised the validity of their findings. The large cohort size reduces the influence of chance and the regular contact maintained between the practitioners and the participants minimizes the potential for recall bias. In all, this study points out that the key factors that need to be taken into consideration when advising women about alcohol consumption during pregnancy are: what the official guidelines are, prenatal alcohol consumption and concomitant smoking and illicit drug use. If these risks can be minimised, the likelihood of pregnant women endangering their foetus with alcohol consumption will also be minimised.

Furthermore, research conducted by Pfinder et al. explored the influence of educational differences and levels of prenatal alcohol exposure21. This study involved 4,885 women and the results showed that women with a higher education had an increased risk of continued drinking throughout early pregnancy and restarting drinking in late pregnancy21. The use of a multivariate regression model to adjust for confounding and a high response rate maximise the relevance of the results with regards to the whole population. However, as with many studies in this field of research, this study was self-reported and so the results may be influenced by recall bias. Although this study accounted for many factors, including physical and psychological problems, to try and explain this phenomenon, a large proportion of the educational differences is still unexplained. The role of cultural factors and social norms may play a crucial role but further research is needed in this area to determine the true causes.

As demonstrated from the aforementioned papers, social factors seem to play a key role in the prevalence of antenatal alcohol drinking. However there is currently limited literature available in this area and more research is necessary for specific and significant causes to be identified and rectified.

GUIDELINE RECOMMENDATIONS

There is a need for clarification in the current guidelines with the Royal College of Obstetricians and Gynaecologists (RCOG) promoting abstinence of alcohol during pregnancy22. The Government guideline also agrees with the RCOG stance, but currently states that pregnant women can drink one to two units of alcohol once or twice a week. The Department of Health justifies this position by stating that consuming alcohol during conception or binge drinking (defined at 7.5 units of alcohol in a short time period) 23

throughout pregnancy should be avoided24. The National Institute for Health and Care Excellence (NICE) recommend avoiding alcohol during the first trimester – the first three months of pregnancy – to reduce the risk of miscarriage23. The lack of consistent guidance is concerning for both women of childbearing age and health professionals advising and caring for these women.

When analysing the literature surrounding the effects of alcohol consumption during pregnancy on the unborn child, it is important to retain perspective on why we need to understand the latest research. Ultimately, physicians need to consolidate the results of a broad range of findings on the topic into one, easy to explain guideline for pregnant women and those trying to conceive. Furthermore, those at NICE need to be able to make sense of the evidence in order to provide “national guidance and advice to improve health and social care” 25 for the Department of Health. The Department of Health can then release this advice to the public.

The current Government guidelines are in line with those of the Royal College of Obstetrics and Gynaecology (RCOG), however NICE takes a slightly different stance on the issue. RCOG and the Department of Health agree that “the only way to be absolutely certain that your baby is not harmed by alcohol is not to drink at all during pregnancy or while… trying for a baby” 26,27. Both recommend a maximum limit for alcohol consumption, if the mother does decide to drink some alcohol. Conversely, NICE makes abstinence a recommendation only for the first three months of pregnancy. In section 1.3.9.1, pregnant women and women planning a pregnancy “should be advised to avoid drinking alcohol in the first 3 months of pregnancy if possible because it may be associated with an increased risk of miscarriage”28. Further NICE guidelines suggest the maximum amount of alcohol pregnant mothers should drink if they can’t abstain totally, so confusingly does not recommend abstinence for the entire pregnancy. All three bodies – NICE, Department of Health, RCOG – agree that if pregnant women do choose to consume alcohol, they should not consume more than 1-2 units of alcohol on one or two occasions a week. The NHS, in its leaflet titled ‘Alcohol and Pregnancy’, agrees and disseminates this same information while explaining the potential mechanisms and consequences of risk of harm to the foetus29. It is important that any physician charged with the care of a pregnant patient is clear that all guidelines recommend abstaining from alcohol – whether for the first trimester or the whole pregnancy period.

Most economically developed countries, such as Australia, Canada, USA and Denmark, recommend avoiding alcohol completely during pregnancy30. The differing factor between them was whether they made a recommendation for if the mother does not choose to stop consuming alcohol completely. On the one hand New Zealand and France, for example, do not offer a limit to which women can drink without excessive damage to the unborn foetus. On the other hand, Switzerland, the UK and Australia recommend no more than two ‘standard drinks’ (units or 10g of alcohol) on no more than two occasions a week.

In our opinion, complete abstinence should unequivocally be the recommendation for pregnant mothers in the UK. In light of the evidence we have reviewed, we believe that advising a quantity of alcohol that can be consumed if the mother does not abstain fully can be confusing and implies that there is a safe limit. While it is difficult to implement and may seem like an insignificant differentiation to make, it is imperative that pregnant women know that drinking alcohol at any level may cause harm to the developing foetus.

CONCLUSION

Clarification is urgently required by health professionals for a nationally agreed, evidence based guideline on alcohol consumption in pregnancy. This would enable women who are trying to conceive or currently pregnant to make an informed choice regarding their decision to drink alcohol during pregnancy 11. Recently, in agreement with our own findings, a BBC article stated that doctors and campaigners would also prefer stronger guidelines. In an open letter by 12 directors of public health they said ‘the safest option is an alcohol free pregnancy…this needs to be the advice given during all stages of pregnancy from conception to birth by all healthcare professionals.’31 From the evaluation of the evidence we have gathered during our literature review we also concluded that guidelines advocating abstinence should be implemented due to the significant negative effects of alcohol on the foetus at all stages of development.

To determine causation, multiple repeated studies are required to provide reliable, widely applicable results. This topic has been thoroughly researched and we appraised a number of studies from a few countries by different researchers to strengthen the validity of our conclusions. Additionally we considered papers that looked at varying levels of alcohol consumption from low to heavy drinking, as well as binge drinking.

Evidence demonstrating the harmful effects of binge drinking during pregnancy on the foetus is prominent. However there is variation in the categorisation of the different levels of alcohol amongst some papers and guidelines. While our society tends to attribute binge drinking to reckless adolescents, it is important that women of childbearing age understand that ‘binging’ is exceeding a certain level of alcohol consumed at one time (which should be clearly demarcated)32. As binge drinking occurs in people of all ages and within homes, a greater level of public education and awareness explaining what constitutes binge drinking and its detrimental effects is required.

We have found the evidence surrounding antenatal drinking and its negative effects, such as SGA and a low Apgar score, to be strong9. The correlation between heavy drinking and other negative factors such as smoking and neglect after birth10 suggests that a reduction in alcohol consumption during pregnancy may have longer lasting positive effects. This is an area for potential future research.

Alcohol consumption in pregnancy can have negative short and long-term effects on the child. Short-term effects include reduced birth weight, lower birth percentile and increased risk of preterm birth5. At birth, babies are identified as having FASD through detection of six clinical features. A reliable study established that one drink per day on average increases the risk of five of six clinical features of FASD4. To add to this, one of the significant adverse long-term impacts of alcohol consumption in pregnancy is an impaired intellectual ability1. A study looking into this impairment entailed parents and teachers completing BRIEF score forms. This subsequently determined that heavy or binge drinking during pregnancy decreased cognitive ability and executive functions in 5 year olds13. The long-term consequences were further demonstrated in a longitudinal study showing moderate levels of maternal alcohol consumption deleteriously impact children’s intellectual ability, learning capacity and attention-span at 14 years of age16. Although one study concluded that light and moderate drinking during the first

trimester did not negatively influence childhood behaviour, its design had a number of limitations. Whilst there is a strong concordance between the conclusions of most of the articles in this field, further longitudinal studies examining the effect of low to moderate alcohol consumption on children’s intellectual ability and behaviour would strengthen these further.

Two papers we reviewed concluded that any alcohol consumed during pregnancy can lead to changes in brain volume and composition14,15. Although both studies had very small sample sizes due to the complexity of the measurements taken, many confounding factors and potential sources of bias were accounted for. This emphasises the potential for harmful foetal effects with any level of alcohol consumption during pregnancy, even if the physical appearance of the child does not make them initially obvious.

There are a wide variety of factors that contribute to the risk of a woman continuing to drink alcohol during pregnancy. In Australia, during the time-period of one study that was carried out, the guidelines were altered from abstinence to low levels and the reverted back to abstinence. When women were not told abstain, the likelihood of them consuming alcohol, increased by a factor of 1.618. This shows just how significantly the relevant guidelines affect women’s behaviour and so indicated that a change in this country’s guidelines to advocating abstinence could lead to a reduction in alcohol consumption during pregnancy. Additionally it is vital that all women receive the same advice and support, without any prejudice from health professionals towards women who drink throughout pregnancy.

There is no definitive test to measure a woman's actual alcohol consumption because alcohol is rapidly metabolised with no measurable trace left. This information is only available from the reports of the prospective-mothers, which is vulnerable to recall bias and under-reporting. Currently there is an on-going court case with a local authority claiming for compensation from the Criminal Injuries Compensation Scheme (a government funded organisation) for the harm done to a child due to the mother’s high levels of alcohol consumption throughout her pregnancy.33 The reasoning for this is the notion that the compensation would improve the child’s level of support and quality of life. However, although compensation would be of benefit, there is a risk that this prosecution could lead to the criminalisation of harmful alcohol consumption during pregnancy. This could then lead to a more drastic level of under-reporting in pregnant women and so less women would get the help they require abstaining from alcohol.

At present the chief medical officer for England is reviewing alcohol guidelines, with a new draft expected next year31. As a group we strongly believe that these guidelines should advise abstinence from alcohol during pregnancy. Many of the studies we looked into found a significant association between alcohol during pregnancy and harmful effects on the child. This measure has the potential to improve the health of many children in the future and reduce the burden on the NHS and social services to manage the associated problems. While people can feel the government is impinging on their right to personal choice it is ultimately the state services who have to assist when difficulties arise from their decisions. It has been clearly shown that a government’s guidelines impact the level of drinking in pregnant women. Alcohol consumption during pregnancy is a serious, prevalent public health issue that needs to be tackled in this country. A strong stance advocating abstinence in the guidelines would benefit multiple levels of society and future generations.

CRITICAL APPRAISAL

Objective: Clearly stated as ‘to examine fetal outcomes of mothers with an alcohol-related diagnosis.’

Study population: Aboriginal and non-Aboriginal women in Western Australia between 1983 and 2007 with births in the Midwives Notification System (MNS).

Study design: Population based-cohort study.

Size of study: 13807 non-Aboriginal, 9766 Aboriginal infants in case cohort, mothers had an alcohol related diagnosis, and 40148 non-Aboriginal, 20643 Aboriginal infants in comparison cohort, mothers without alcohol related diagnosis.

Intervention: Measurements were birth weight, Apgar score and preterm birth. Cases and controls were compared on these fetal outcomes with two controls per Aboriginal case and three controls per non-Aboriginal case mother.

Randomisation and blinding: This study utilised no blinding. All mothers on the WA Data Linkage System identified as exposed to alcohol and their infants on the MNS were included, therefore eliminating selection bias despite lack of randomisation. Comparison cohort were selected randomly, provided they had no recorded alcohol-related diagnosis.Statistical Tests: Frequency matching ensured compared individuals had similar maternal age at time of birth and same year of birth for each race. An enter model accounted for many relevant confounding factors. Chi square demographics enabled comparison of maternal qualities and foetal effects between groups. These are all appropriate tests as they increase comparability between cases and controls.

Outcome measure: Results measured were small for gestational age (SGA), preterm birth (moderate and very), and low-Apgar score, presented as adjusted relative risk and 95% confidence intervals. The population-attributable fraction of alcohol on adverse foetal outcomes was assessed. Aim of the study is fulfilled as measurements have quantifiable outcomes.

Main Results: Any alcohol diagnosis and alcohol diagnosis during pregnancy increased number of SGA infants, pre-term births and neonates with low-Apgar score compared to controls. Only any alcohol diagnosis during pregnancy in non-Aboriginals' results are presented below due to our project topic:

● non-Aboriginal – SGA–aRR-1.79, 95%CI-1.42–2.16● Preterm birth - moderate aRR-1.81, 95%CI-1.45–2.27, very aRR-2.57, 95%CI-1.54–4.27● Apgar Score – aRR-2.14, 95%CI-1.31–3.50

Sources of Bias: Health services could fail to detect women with episodic pattern of binge drinking and there is a lack of service data for Aboriginal-specific health services, and rural drug and alcohol services. Therefore misclassifications could have occurred, likely to bias the study outcomes towards the null. Selection bias may arise through under-representation of heavy pregnant drinkers, due to complex situations resulting in moving during pregnancy. Measurement bias may have resulted through using population attributional fraction as it only accounts for one risk factor contributing to adverse outcome, excluding confounding factors.

Further comments: This study agrees with other papers that heavy maternal drinking increases risk of SGA and preterm delivery. It contradicts other studies by suggesting that alcohol consumption is more prevalent in lower socioeconomic classes and those with poor access to antenatal care.

Conclusion: We believe the results of this study are valid due to a large sample size, reducing the probability that results occurred by chance. Any bias would have decreased the association towards the

null, therefore results are still reliable. Accounting for many confounding factors increases the likelihood that association is genuine, not caused by an independent factor. A definite determination of causation requires consistency, despite agreement with other studies more are still needed to strengthen the association established in this study.

INFORMATION SEARCH REPORT

Before the first meeting individuals in the group looked for information on the topic of the project to give themselves an overview on the topic. The personal tutor also provided two review articles on for the group to further familiarize themselves on.

After members of the group found three clinical trials each to analyse. This was done using the search engine OVID that utilises the Medline database. OVID allows search term to be linked as to only show articles that included each of the terms. It also allows limits to be placed to only include relevant information as shown below.

Ovid was used as shown in the worked example below:1. Pregnancy/ (715572)*2. Alcohols/(568413)*3. Congenital Abnormalities/(30793)*4. 1 and 2 and 3 (64)5. Similar to The effects of alcohol consumption during pregnancy. (5947)*6. limit 5 to (humans and clinical trial, all and last 5 years) (82)*

*Number of articles found

Three key terms (pregnancy, alcohol and congenital abnormalities) that were relevant to the subject of the project were searched. These were then combined so that only articles that featured all three of the terms were included leaving 64 articles (#4). An individual article was chosen ‘The effects of alcohol consumption during pregnancy’ as relevant to the project. Articles similar to this were searched for giving 5947 articles (#5). This was then limited to only clinical trials conducted using humans and that were conducted in the last five years so all articles found contained recent information relevant to humans leaving 82 articles (#6). These were then manually sifted to find articles most relevant to the project. All articles found were available in full text as they were carried out on Edinburgh University computers so finding full text articles was not an issue.

CONTRIBUTIONS

Dr Sunit Rane MBBS, MRCOG, RCOG/RCR - Consultant Obstetrician and Gynaecologist

Hannah Brutin - 2nd Year Medical Student from Linlithgow, West Lothian.Background research; group critical appraisal; conclusion.

Rebecca Dru - 2nd Year Medical Student from High Wycombe, Buckinghamshire.Background research; guidelines section of main body; editing of website.

Hannah Malcolm - 2nd Year Medical Student from Houston, Glasgow.Background research; main body.

Ben McLean - 2nd Year Medical Student from Barrhead, East Renfrewshire.Background research; main body.

Robbie Miller - 2nd Year Medical Student from Ayr, Ayrshire. Background research; information search report; references.

Felicity Robinson - 2nd Year Medical Student from Bolton, Lancashire.Background research; main body.

Sarah Wordie - 2nd Year Medical Student from Huntly, Aberdeenshire.Background research; Introduction (main and for each section); Methods of prevention.

REFERENCES1. National Institute for Health and Clinical Excellence. Antenatal Care. (2008) [cited 2014-10-20]

available from: URL:http://www.nice.org.uk/guidance/cg62/chapter/1-guidance#lifestyle-considerations (online leaflet)

2. O'Leary, C., Halliday, J., Bartu, A., D'Antoine, H. and Bower, C. (2013). Alcohol-use disorders during and within one year of pregnancy: a population-based cohort study 1985-2006. BJOG, 120(6), pp.744-753.

3. Ethen, M., Ramadhani, T., Scheuerle, A., Canfield, M., Wyszynski, D., Druschel, C. and Romitti, P. (2008). Alcohol Consumption by Women Before and During Pregnancy. Matern Child Health J, 13(2), pp.274-285

4. Education and Health standing Committee, Parliament of Western Australia. Fetal alcohol disorder spectrum: the invisible disability. (2012). [cited 17 November 2014]. Available from: http://www.parliament.wa.gov.au/parliament/commit.nsf/(Report+Lookup+by+Com+ID)/1740F63B37A1314A48257A7F000766DD/$file/Final+FASD+Report+with+signature.pdf

5. British Medical Association. Foetal Alcohol Disorders - A guide for health care professionals. BMA. 2007;.*****

6. Sawada Feldman H, Lyons Jones K, Lindsay S, Slymen D, Klonoff-Cohen H, Kao K et al. Prenatal Alcohol Exposure Patterns and Alcohol-Related Birth Defects and Growth Deficiencies: A Prospective Study. Alcoholism: Clinical and Experimental Research. 2012;36(4):670-676.

7. Nykjaer C, Alwan N, Greenwood D, Simpson N, Hay A, White K et al. Maternal alcohol intake prior to and during pregnancy and risk of adverse birth outcomes: evidence from a British cohort. Journal of Epidemiology & Community Health. 2014;68(6):542-549.

8. The Fact About Drinking and Pregnancy [Internet]. 2013 [cited 12 November 2014]. Available from: https://www.drinkaware.co.uk/check-the-facts/health-effects-of-alcohol/fertility-and-pregnancy/alcohol-and-pregnancy

9. Kelly Y, Sacker A, Gray R, Kelly J, Wolke D, Quigley M. Light drinking in pregnancy, a risk for behavioural problems and cognitive deficits at 3 years of age?. International Journal of Epidemiology. 2008;38(1):129-140.

10. BabyCenter. Drinking alcohol during pregnancy [Internet]. 2014 [cited 12 November 2014]. Available from: http://www.babycenter.com/0_drinking-alcohol-during-pregnancy_3542.bc

11. Srikartika V, O'Leary C. Pregnancy outcomes of mothers with an alcohol-related diagnosis: a population-based cohort study for the period 1983-2007. BJOG: Int J Obstet Gy. 2014;:n/a-n/a.

12. O'Leary C, Jacoby P, Bartu A, D'Antoine H, Bower C. Maternal Alcohol Use and Sudden Infant Death Syndrome and Infant Mortality Excluding SIDS. PEDIATRICS. 2013;131(3):e770-e778.

13. McCarthy F, OʼKeeffe L, Khashan A, North R, Poston L, McCowan L et al. Association Between Maternal Alcohol Consumption in Early Pregnancy and Pregnancy Outcomes. Obstetrics & Gynecology. 2013;122(4):830-837.

14. Sayal K, Heron J, Golding J, Alati R, Smith G, Gray R et al. Binge Pattern of Alcohol Consumption During Pregnancy and Childhood Mental Health Outcomes: Longitudinal Population-Based Study. PEDIATRICS. 2009;123(2):e289-e296.

15. Skogerbø Å, Kesmodel U, Wimberley T, Støvring H, Bertrand J, Landrø N et al. The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on executive function in 5-year-old children. BJOG: An International Journal of Obstetrics & Gynaecology. 2012;119(10):1201-1210.

16. Roussotte F, Sulik K, Mattson S, Riley E, Jones K, Adnams C et al. Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders. Human Brain Mapping. 2011;33(4):920-937.

17. Eckstrand K, Ding Z, Dodge N, Cowan R, Jacobson J, Jacobson S et al. Persistent Dose-Dependent Changes in Brain Structure in Young Adults with Low-to-Moderate Alcohol Exposure In Utero. Alcoholism: Clinical and Experimental Research. 2012;36(11):1892-1902.

18. O'Callaghan F, O'Callaghan M, Najman J, Williams G, Bor W. Prenatal alcohol exposure and attention, learning and intellectual ability at 14 years: A prospective longitudinal study. Early Human Development. 2007;83(2):115-123.

19. Robinson M, Oddy W, McLean N, Jacoby P, Pennell C, de Klerk N et al. Low-moderate prenatal alcohol exposure and risk to child behavioural development: a prospective cohort study. BJOG: An International Journal of Obstetrics & Gynaecology. 2010;117(9):1139-1152.

20. Anderson A, Hure A, Forder P, Powers J, Kay-Lambkin F, Loxton D. Predictors of antenatal alcohol use among Australian women: a prospective cohort study. BJOG: Int J Obstet Gy. 2013;120(11):1366-1374.

21. Pfinder M, Kunst A, Feldmann R, Eijsden M, Vrijkotte T. Educational differences in continuing or restarting drinking in early and late pregnancy: role of psychological and physical problems. 2014;.

22. Alcohol and pregnancy: information for you. Royal College of Obstetricians and Gynaecologists [Internet]. 2006 [cited 12 November 2014];. Available from: http://Royal College of Obstetricians and Gynaecologists

23. Nice.org.uk. Antenatal care | 1-guidance | Guidance and guidelines | NICE [Internet]. 2008 [cited 12 November 2014]. Available from: http://www.nice.org.uk/guidance/cg62/chapter/1- guidance#lifestyle-considerations

24. Pregnancy and Alcohol. Alcohol [Internet]. 2008 [cited 12 November 2014];. Available from: http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_085426.pdf

25. Nice.org.uk. Who we are [Internet]. 2014 [cited 3 November 2014]. Available from: http://www.nice.org.uk/about/who-we-are

26. Royal College of Obstetricians and Gynaecologists. Alcohol and pregnancy: information for you [Internet]. 2006 [cited 2 November 2014]. Available from: https://www.rcog.org.uk/globalassets/documents/patients/patient-information-leaflets/pregnancy/alcohol-and-pregnancy.pdf

27. Drinkaware.co.uk. Alcohol and pregnancy [Internet]. 2013 [cited 3 November 2014]. Available from: https://www.drinkaware.co.uk/check-the-facts/health-effects-of-alcohol/fertility-and- pregnancy/alcohol-and-pregnancy

28. Nice.org.uk. Antenatal care [Internet]. 2008 [cited 3 November 2014]. Available from: http://www.nice.org.uk/guidance/cg62/chapter/1-guidance#lifestyle-considerations

29. National Health Service. Pregnancy and Alcohol [Internet]. 2008 [cited 3 November 2014]. Available from: http://webarchive.nationalarchives.gov.uk/20130107105354/http:/www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_085426.pdf

30. Icap.org. International Guidelines on Drinking and Pregnancy [Internet]. 2009 [cited 2 November 2014]. Available from: http://www.icap.org/Table/InternationalGuidelinesOnDrinkingAndPregnancy

31. BBC. 'Stronger warnings needed' over pregnant women drinking’ [Internet]. 2014 [cited 16 November 2014]. Available from: http://www.bbc.co.uk/news/health-2961441 3

32. Telegraph.co.uk. The Big Society can solve the problem of binge drinking [Internet]. 2010 [cited 16 November 2014]. Available from: http://www.telegraph.co.uk/health/7986417/The-Big-Society- can-solve-the-problem-of-binge-drinking.html

33. Theguardian.com. Foetal damage caused by alcohol ‘equivalent to attempted manslaughter’ [internet]. 2014 [cited 16 November 2014]. Available from: http://www.theguardian.com/law/2014/nov/05/foetal-damage-mother-alcohol-manslaughter