Critique 020: New data on effects of alcohol during pregnancy 12 October 2010
Kelly YJ, Sacker A, Gray R, Kelly J, Wolke D, Head J, Quigley MA. Light drinking during pregnancy: still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age? J Epidemiol Community Health 2010; doi:10.1136/jech.2009.103002
Authors’ Abstract
Background This study examines the relationship between light drinking during pregnancy and the risk of socioemotional problems and cognitive deficits at age 5 years.
Methods Data from the nationally representative prospective UK Millennium Cohort Study (N=11 513) were used. Participants were grouped according to mothers’ reported alcohol consumption during pregnancy: never drinker; not in pregnancy; light; moderate; heavy/binge. At age 5 years the strengths and difficulties questionnaire (SDQ) and British ability scales (BAS) tests were administered during home interviews. Defined clinically relevant cut-offs on the SDQ and standardised scores for the BAS subscales were used.
Results Boys and girls born to light drinkers were less likely to have high total difficulties (for boys 6.6% vs 9.6%, OR=0.67, for girls 4.3% vs 6.2%, OR=0.69) and hyperactivity (for boys 10.1% vs 13.4%, OR=0.73, for girls 5.5% vs 7.6%, OR=0.71) scores compared with those born to mothers in the not-in-pregnancy group. These differences were attenuated on adjustment for confounding and mediating factors. Boys and girls born to light drinkers had higher mean cognitive test scores compared with those born to mothers in the not-in-pregnancy group: for boys, naming vocabulary (58 vs 55), picture similarities (56 vs 55) and pattern construction (52 vs 50), for girls naming vocabulary (58 vs 56) and pattern construction (53 vs 52). Differences remained statistically significant for boys in naming vocabulary and picture similarities.
Conclusions At age 5 years cohort members born to mothers who drank up to 1 – 2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of mothers in the not-in-pregnancy group.
Forum Comments
Background: Associations between heavy alcohol consumption during pregnancy and adverse effects on the fetus have been known for decades. The full syndrome (Fetal Alcohol Syndrome, FAS) has devastating effects on the child, with mental retardation, congenital heart defects, and many other abnormalities. While FAS is a result of very heavy alcohol use during early pregnancy, occurring essentially only among alcoholic women, there have been extensive campaigns to condemn any alcohol consumption during pregnancy because a very loosely defined group of conditions have been attributed to alcohol intake during pregnancy. However, the relation of such conditions to moderate drinking (rather than to often-associated illegal drug use, poor socioeconomic status (SES), low education, and other lifestyle factors) has never led to a clear association with alcohol. Further, there has never been a precise definition of FAE, as a lower score on certain cognitive/social functioning testing is called FAE if the mother reports alcohol consumption during pregnancy but something else if the mother does not report any alcohol intake.
There continue to be published articles on the relation of alcohol intake during pregnancy and potential effects on the child, with several within the past three years. Henderson et al1 carried out a systematic review of studies in the literature between 1970 and 2005. They found 14 publications giving relevant data. The authors found no consistent evidence of adverse effects from binge drinking, usually defined as consuming more than 4 drinks on an occasion. The authors conclude: “When a pregnant woman reports isolated episodes of binge-drinking . . . it is important to avoid inducing unnecessary anxiety as, at present, the evidence of risk seems minimal.”1
In an earlier report from the same study as in the present paper, Kelly et al2 compared evidence of behavioral problems or cognitive deficits at age 3 years among the children according to the mother’s drinking during pregnancy. For mothers who reported drinking no more than 1 to 2 drinks/week or 1 to 2 drinks/occasion (termed light drinking in that study), there was no evidence of increased risk. In fact, the risks of many behavioral/cognitive problems were lower among the children of such women. However, as in the present report, there were marked socioeconomic differences associated with women’s drinking (e.g., both abstainers and heavy drinkers tended to have lower education and social status and smoked more than light drinkers). Many of the purportedly “beneficial” effects of light drinking were no longer evident when all of these factors were taken into consideration.
Alihu et al3 investigated the association between maternal alcohol intake in pregnancy and the occurrence of early stillbirth using a retrospective cohort analysis of singleton births in Missouri that occurred in the period 1989 through 1997 (N=655,979). Among mothers who consumed alcohol during pregnancy, the stillbirth rate was 8.3 per 1,000. Mothers who consumed alcohol while pregnant were 40% more likely to experience stillbirth as compared with nondrinking mothers (adjusted hazards ratio=1.4, 95% confidence interval: 1.2-1.7). A dose-response relationship was evident; no significant effect was seen for mothers who consumed 4 or fewer drinks/week, but those reporting 5 or more drinks per week during pregnancy experienced a 70% elevated risk of stillbirth compared with nondrinking mothers (adjusted hazards ratio=1.7; 95% confidence interval: 1.0-3.0). The authors concluded that maternal drinking during pregnancy is associated with an increased risk of early stillbirth, with significant increases occurring among women reporting 5 or more drinks per week.
D’Onofrio et al4 provided additional evidence that increased amounts of alcohol consumption during a pregnancy (especially when associated with binge-drinking and other measures of alcohol misuse) are associated with an increased risk of maternal-reported conduct problems (CPs) in the child, and such an association did not change when adjustment was made for potential confounders. (The strongest predictors of CPs were smoking, heavy alcohol use, marijuana or cocaine use, having children with different fathers, and young age at first child.) No effect of alcohol was found on maternal-reported attention/impulsivity problems in the child. The study did not have adequate numbers to estimate if there is a threshold effect of prenatal alcohol exposure on the risk of CPs in the children, but their data suggest that the amount of alcohol consumed during pregnancy, if any, should be very light.
In a recent report by Chiodo et al5, some abnormalities were noted in the children of mothers over the age of 30 who consumed alcohol during pregnancy. It appears that the authors used a linear model and were not able to assess for a threshold level for effects. Further, they state in their discussion: “One study limitation needs to be addressed, potentially poor generalizability. The current cohort included only low-SES urban African American women and their children. We should also note that although significant, the effect size is small (Cohen’s F2 = 0.03 and 0.02 for b and errors of commission respectively). For these attention measures, the alcohol-maternal age interaction term accounts for 3% (b) and 2% of the variance (errors of commission). In addition, the cohort in which the initial maternal age effects were obtained (Jacobson et al., 1994) had similar homogenous demographics. Thus, these findings need to be reassessed in more heterogeneous populations. We also note the lack of significance in teacher-reported attention findings (i.e., the TRF).”5
Comments on the present paper: There are a number of important strengths of this study. It is based on a very large population-based sample with excellent response to recruitment. It was able to separate women who were teetotalers from those who consumed alcohol prior to pregnancy but not during pregnancy. It used reasonable instruments to assess behavioral and emotional problems and cognitive ability in the child at age 5 years. It had data on a very large number of “explanatory factors” (e.g., smoking, education, income, occupation, number of children in family, and parental discipline strategies) that are known to affect outcomes in the child. It used appropriate analysis techniques.
The results indicate primarily that the children of women who reported light (no more than 1-2 units of alcohol per week or per occasion) or moderate (no more than 3-6 units per week or 3-5 units of alcohol per occasion) drinking did not show evidence of impairment. There was some evidence that the male children of women reporting “heavy/binge” drinking during pregnancy (7 or more units per week or 6 or more units per occasion) had a tendency for poorer behavioral scores, but the effects were less clear among female offspring. It is interesting that for boys the crude estimates of effect were not very different from estimates fully adjusted by a large number of potential confounders; this indicates that the associated lifestyle factors did not have a large effect on the association of alcohol with behavioral and cognitive outcomes among boys in this study. There was greater attenuation of the effects from such factors seen among girls.
It is clear from the data presented that the children of women reporting light drinking during pregnancy had outcomes as good as or better than those of women reporting not drinking during pregnancy. As pointed out by the authors, however, women who reported light drinking during pregnancy were by far the most advantaged socio-economically and educationally. Such women may well have had other lifestyle factors that would have reduced the risk of a child with problems, factors that could have been inadequately adjusted for in the analysis (as is always the case in observational studies). In fact, the authors state that “it is likely that social circumstances to a large part are responsible for the relatively low rates of subsequent behavioural difficulties and the cognitive advantage in children whose mothers were light drinkers.” Overall, the clear message is that occasional or light drinking during pregnancy did not result in poorer performance on testing in the children at 5 years of age in this cohort.
Additional comments by Forum members on the present study: It has been shown in rats that exposure to red wine in the mother during pregnancy is less toxic for liver and brain of the fetus than is exposure to ethanol,6 so differences by type of beverage consumed (not reported in the present study) could play a role. It has also been suggested that there is the possibility that light drinking during pregnancy could favorably affect endothelial function in the fetus, but the potential dangers of adverse effects from alcohol preclude a clinical trial to test for this.
Another Forum member pointed out that it is always impossible to properly account for all possible confounders in a study like this. “The authors make a valiant attempt looking at maternal factors, child birth weight, socioeconomic factors, parenting factors, etc. Women in the light drinker group during pregnancy were more advantaged than all other categories including the ‘not in pregnancy’ group. As the authors state, it is likely that social circumstances are responsible for the relatively low rates of difficulties in the group of children whose mothers were light drinkers. However, having said that, this study did not establish any correlation between light drinking during pregnancy and subsequent five-year-old child behavioural difficulty or cognitive impairment. This is consistent with much recent literature where the attempts to find an alcohol dose where intrauterine exposure to alcohol begins to produce fetal alcohol syndrome-like signs has never been particularly convincing. Given that moderate people do moderate things, what is fascinating is that it would have been thought that the ‘moderate people’ in this study would be likely to adhere to the commonly accepted advice that it is unwise to drink in pregnancy. The socio-economically advantaged women in this study who were light drinkers obviously did not adhere to this advice.”
Another Forum member emphasized how the association between light drinking during pregnancy and poor outcomes in the child is loaded with emotions and difficult to define precisely from observational data. A clinical trial to seek a “safe” level of drinking during pregnancy is not a possibility. He adds: “As an example of the difficulties in providing balanced guidelines for drinking in pregnancy, in Denmark the official advice has changed three times in the past 20 years: from no alcohol allowed, to up to 5 drinks/week, to no alcohol allowed.”
“Paternalism” in recommendations for pregnant women: Colin Gavaghan (an ethicist from the School of Law, Glasgow, Scotland) has pointed out potential dangers of over-strict recommendations for women during pregnancy7. He argues that a paternalistic approach (“We know what is best for you”) “is inappropriate and is demeaning to pregnant women. We should just provide balanced information and admit where there is still uncertainty.” Further, he is afraid that such a message about the dangers of any alcohol during pregnancy “risks alienating and worrying women who are at very low risk, while having a negligible impact on high-risk drinkers who ignored the previous guidelines anyway. A total abstinence position may backfire, serving to erode the trust the public places in medical advice.”7
Gavaghan adds that “the question of what information and advice healthcare practitioners ought to present to pregnant women, or prospectively or potentially pregnant women, in a situation of uncertainty is one to which healthcare ethicists may have a contribution to make.” He argues that “the total abstinence policy advocated by the UK’s Department of Health, and even more stridently by the British Medical Association, sits uneasily with recent data and is far from ethically unproblematic. The ‘precautionary’ approach advocated by these bodies displays both scant regard for the autonomy of pregnant and prospectively pregnant women and a confused grasp of the principles of beneficence and non-maleficence.”7
References from Forum Review:
1. Henderson J, Kesmodel U, Gray R. Systematic review of the fetal effects of prenatal binge-drinking. J Epidemiol Community Health 2007;61:1069–1073.
2. Kelly Y, Sacker A, Gray R, Kelly J, Wolke D, Quigley MA. Light drinking in pregnancy, a risk for behavioural problems and cognitive deficits at 3 years of age? Int J Epidemiol 2009;38:129-140.
3. Aliyu MH, Wilson RE, Zoorob R, Chakrabarty S, Alio AP, Kirby RS, Salihu HM. Alcohol consumption during pregnancy and the risk of early stillbirth among singletons. Alcohol 2008;42:369-374.
4. D’Onofrio BM, Van Hulle CA, Waldman ID, Rodgers JL, Rathouz PJ, Lahey BB. Causal inferences regarding prenatal alcohol exposure and childhood externalizing problems. Arch Gen Psychiatry 2007;64:1296-1304.
5. Chiodo LM, da Costa DE, Hannigan JH, et al. The Impact of Maternal Age on the Effects of Prenatal Alcohol Exposure on Attention. Alcohol Clin Exp Res 2010 Oct;34(10):1813-21. doi: 10.1111/j.1530-0277.2010.01269.x.
6. Fiore M, Laviola G, Aloe L, di Fausto V, Mancinelli R, Ceccanti M. Early exposure to ethanol but not red wine at the same alcohol concentration induces behaviioral and brain neurotrophin alterations in young and adult mice. Neurotoxicology 2009;30:59-71.
7. Gavaghan C. ‘‘You can’t handle the truth’’; medical paternalism and prenatal alcohol use. J Med Ethics 2009;35:300–303. doi:10.1136/jme.2008.028662.
Forum Conclusions
Scientific data continue to indicate that higher intake of alcohol during pregnancy may adversely affect the fetus, and could lead to very severe developmental or other problems in the child. However, most recent publications show little or no effects of occasional or light drinking by the mother during pregnancy. They also demonstrate how socio-economic, education, and other lifestyle factors of the mother may have large effects on the health of the fetus and child; these must be considered when evaluating the potential effects of alcohol during pregnancy.
The present large, well-done study from the UK found no evidence of adverse effects from light drinking by the mother during pregnancy in terms of behavioral and emotional problems or cognitive dysfunction in the children at age 5 years. We conclude that while drinking during pregnancy should not be encouraged, there is little evidence to suggest that an occasional drink by the mother is associated with harm.
On the other hand, as stated by a Forum member, “Moderate drinking is not an imperative, and suspending alcohol intake for nine months should not be a big problem; cardiovascular protection should not be affected by avoiding alcohol during pregnancy.” The Forum member adds, “Until science provides even stronger evidence, we should not encourage pregnant women to drink, but obviously should not terrorize those pregnant women who are occasional or light drinkers.”
* * *
Comments included in this critique by the International Scientific Forum on Alcohol Research were provided by the following:
Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis.
Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy.
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.
Francesco Orlandi, MD, Dept. of Gastroenterology, Università degli Studi di Ancona. Italy.
Ross McCormick PhD, MSC, MBChB, Associate Dean, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona, USA.
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA.
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.
Giovanni de Gaetano, MD, PhD, Research Laboratories, Catholic University, Campobasso, Italy
Addendum
After the above critique was prepared, a new paper has been published on the topic by O’Leary et al in the journal Pediatrics1.
In a population-based study of 4,714 births in Western Australia, assessment of alcohol consumption prior to pregnancy and during each trimester separately was obtained at 3 months after the birth of the child. Consumption of alcohol throughout pregnancy and consumption during each trimester was defined as follows: (a) abstinent: no drinking during pregnancy; (b) low drinking: less than 7 standard drinks, and, on any one day, no more than 2 standard drinks); (c) moderate drinking: ≤70 g of alcohol per week (with the majority consuming 21 to 49 g per occasion); women who engaged in binge drinking of ≥50 g per occasion less than weekly were included in the moderate group; and (d) heavy drinking: women who engaged in binge drinking 1 or 2 times per week or more than twice per week and heavy drinkers who consumed < 5 standard drinks per occasion (the majority consumed >20 g of alcohol per occasion) but >70 g per week.
The association between women in each category was related to the presence of a birth defect and to the presence of an “alcohol-related birth defect” (ARBD) in the child. The key findings were as follows:
(1) Fewer than one-half (40.8%) of women abstained throughout pregnancy.
(2) Almost one-half of the infants diagnosed as having an ARBD occurred in women who had not consumed alcohol during the first trimester (a period in pregnancy when most organ development in the fetus occurs). This led the authors to state “These findings raise question about the clinical validity of labeling specific birth defects as ARBDs.”
(3) After adjustment for maternal age, marital status, parity, income, smoking during pregnancy, and drug use during pregnancy, in comparison with women who were abstinent during pregnancy (OR = 1.0), there was no evidence of an increase in risk of any birth defect among women classified as low [OR 0.84 (95% CI 0.62-1.13)] or moderate [OR 0.85 (95% CI 0.55-1.29)] drinkers during the first trimester. Women classified as heavy drinkers during the first trimester had a trend toward an increase in risk of a child with a birth defect [OR 1.28 (95% CI 0.69-2.38).
(4) Adjusted values for ARBD, versus women abstinent during pregnancy (OR 1.0), were OR 1.11 (95% CI 0.52-2.39) for low drinking during the first trimester and OR 4.57 (95% CI 1.46-14.26) for heavy drinking during this period. (There were too few cases for estimates for the moderate drinking category.)
Comment: This study did not find evidence of an increase in any birth defect or an alcohol-related birth defect for mothers reporting low or moderate drinking during pregnancy. There was an increase in the risk of ARBD for women classified as heavy drinkers during the first trimester, although the number of children with a defect born of heavy drinkers during the first trimester was very small (2 cases of ARBD in the moderate category and 5 cases of ARBD in the heavy category). Overall, the results of this study are similar to those of the study by Kelly et al2 with the suggestion of an increased risk with heavy drinking.
References:
- O’Leary CM, Nassar N, Kurinczuk JJ, de Klerk N, Geelhoed E, Elliott EJ, Bower C. Prenatal Alcohol Exposure and Risk of Birth Defects Pediatrics 2010;126;e843-e850; DOI: 10.1542/peds.2010-0256
- Kelly YJ, Sacker A, Gray R, Kelly J, Wolke D, Head J, Quigley MA. Light drinking during pregnancy: still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age? J Epidemiol Community Health 2010; doi:10.1136/jech.2009.103002
Comment by R. Curtis Ellison, MD; Boston University School of Medicine, Boston, MA, USA