Critique 207: Effects on birth weight and risk of preterm birth of light-to-moderate drinking during pregnancy – 2 November 2017

Strandberg-Larsen K, Poulsen G, Bech BH, Chatzi L, Cordier S, MT Grønning Dale, Fernandez M, Henriksen TB, Jaddoe VWV, Kogevinas M, Kruithof CJ, Søndergaard Lindhard M, Magnus P, Aagaard Nohr E, Richiardi L, Rodriguez-Bernal CL, Rouget F, Rusconi F, Vrijheid M, Nybo Andersen A-M.  

Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts. Eur J Epidemiol 2017, pre-publication; DOI 10.1007/s10654-017-0323-2

Authors’ Abstract

Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias.

In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time.

In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth.  The analyses restricted to women without reproductive experience revealed similar results.

Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011.  Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake.

The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity.

Forum Comments

There is no question that heavy drinking during pregnancy can lead to adverse health effects in the fetus, with commonly described effects being an increase in risk of preterm birth and lower birth weight. However, a number of recent studies have shown that light-to-moderate intake of alcohol in pregnant women has not shown these adverse effects on birth weight or gestational age.

The present study is based on individual-level analysis of alcohol consumption during pregnancy for a total of about 180,000 women from studies in Denmark, Norway, the Netherlands, Spain, Italy, France, and Greece, with the outcomes being risk of preterm birth, having an infant being small for gestational age (SGA), and low birth weight.

Comments from individual Forum members

Reviewer Ellison noted: “In my opinion, key findings from this multi-center include the following:

1. The reported frequency of alcohol consumption during pregnancy in the cohorts studied has decreased dramatically in recent decades (from approximately 50% of women studied prior to 2000, to 39% in 2000-2004, to 14% in 2005-2011); thus, policy statements that women should not consume alcohol during pregnancy seem to be working in these countries.
2. As for effects of alcohol intake during pregnancy, reporting of up to 6 drinks/week, as compared to abstaining, was associated with a lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. A greater amount of reported alcohol intake was associated with higher risk of term SGA and lower birth weight and, but no increase in the risk of preterm birth.
3. Interestingly, birth weight associated with drinking was reduced in studies prior to 2000, but in the period 2005-2011 birth weight increased with increasing alcohol intake; the authors state that they are not aware that there are physiologic mechanisms by which alcohol intake should increase birth weight, and they assumed the effect was due to confounding. They could not determine whether the increase in birth weight from light drinking was due to unmeasured confounding which changed over time or due to cohort heterogeneity. Forum members agreed that the measured increase in birth weight for light drinkers in certain time periods is probably related to confounding, e.g., by education or other indices of socio-economic status.”

Members noted that the alcohol consumption during pregnancy in this analysis was very light, as only 7% of women reported 2 or more drinks per week. Also, the investigators found that a history of previously having an infant with low birth weight or other problems attributed to alcohol consumption did not modify the frequency of drinking during pregnancy (this was evaluated by sensitivity analyses limited to first-time pregnancies).

Several members noted that this study had no data on other potential adverse effects of alcohol consumption during pregnancy (some of which may not be detected until the child is older). However, the study results support recent scientific data indicating that, while alcohol consumption is not recommended for pregnant women, those who have an occasional drink or other light drinking may not have to worry about preterm or SGA birth or decreased birth weight of their infant related to the alcohol consumption; heavier intake is associated with lower birth weight and a higher risk of an infant being SGA, but no increased risk of preterm birth was seen in this study.

Forum member Finkel added: “This paper is likely to raise a few hackles, as many agencies have strongly condemned any alcohol intake during pregnancy.  While this study is hardly definitive, it squares with other studies of the subject relationships, another sort of J-shaped curve.”

Reviewer Van Velden agreed: “This is a very sensitive area, but I think that the above summary statements are well-balanced. Responsible drinkers tend to be health-conscious, and will also eat a healthy diet, do some exercise and be non-smokers – there are many confounders.  However, we must realize that a glass of wine with poly-phenols with a balanced meal during pregnancy is probably harmless, while heavy alcohol intake (and there are many in my country, with a very high incidence of fetal alcohol syndrome, or FAS) by people who tend to drink poor quality wine, do not consume healthy foods, and have other diet deficiencies such as iron deficiency, low folate intake, and high-refined CHO diets, may have adverse effects.”  Other Forum members added that many other confounders, especially associated with a low socio-economic status (including heavy smoking, concomitant drug use, poor pre-natal care, etc.) also contribute.

Reviewer Skovenborg agreed with the above comments, and added: “Obviously the policy advice that ‘the safest choice for pregnant women is to abstain from alcohol during pregnancy’ is uncontroversial; however, the abstinence message needs to be presented in a balanced and rational manner to prevent unintended negative consequences. Over-interpretation of risk leading to comments such as ‘even one drink can harm your baby’ can generate more harm than good, as described by Armstrong and Abel.”

Armstrong and Able have suggested that “Concern about any alcohol during pregnancy has escalated beyond the level warranted by the existing evidence, and that FAS has taken on the status of a ‘moral panic’.” Forum members have noted reports of some women who became so frightened because they had consumed even one or two drinks before realizing that they were pregnant have considered therapeutic abortion, which would be excessive given our current knowledge on the topic.

Forum member Waterhouse commented: “The authors should have compared FAS rates to the changing alcohol consumption rates over this period of study to see whether or not the reduction in alcohol consumption by pregnant women has had any detectable benefit. That aside, I would agree with the others that this data confirms other reports showing that occasional light drinking during pregnancy should not raise any concern for the health of the fetus.” Reviewer Ellison added: “I would be surprised if there were any changes in rates of FAS in these cohorts, as the number of very heavy drinkers, confirmed alcoholics, or drug abusers (who are the main women having FAS infants) was extremely low.”

Some appropriate comments were received from Forum member Stockley: “The relationship between alcohol consumption and other pregnancy outcomes apart from FAS is complex, controversial and uncertain, and it difficult for researchers to provide absolute advice based on the literature. Irrespective of advice to the contrary, a percentage, albeit gradually declining, of women continue to consume alcohol during their pregnancy. Accordingly, in addition to recommending abstinence during pregnancy, any advice should also include that pregnant women should ensure that if they do choose to drink, that they never drink to intoxication as there is a significantly increased risk of alcohol-related harm to the developing foetus; alcohol consumption during the first trimester of pregnancy presents the highest risk to the developing foetus.”

Reviewer Boban agreed that we must be cautious in giving recommendations on this topic: “I agree with the ‘precautionary principle’ taken by the Forum, recommending no alcohol during pregnancy as the safest option, despite the fact that a threshold for alcohol related harm to the fetus has not been established. Even more I support the Forum position that dramatization or over-interpretation of risk because of an occasional drink or very light alcohol during pregnancy should be avoided, as it may result in more harm than good.  So, I think that like in all other aspects of everyday life, we just need common sense.”

Forum member Goldfinger stated: “The findings of this report are not of great surprise. Healthy drinking in moderation, even during pregnancy, may continue to produce healthy outcomes, even to the fetus.  Nevertheless, prospective studies on this subject are prohibitive.  There are many specific endpoints that could and should be looked at among drinking hosts, such as endothelial function, that could be tested in children of parents who both consumed and resisted alcohol during pregnancy.  However, for now, and even recognizing a number of health benefits (possibly even to the fetus), the medical community cannot risk any recommendation for women to consume alcohol during pregnancy because of the potential for risk of fetal-alcohol complications in an irresponsible host.”

Reference from Forum critique

Armstrong EM Abel EL. Fetal alcohol syndrome: the origins of a moral panic.  Alcohol Alcohol 2000;35:276-282.

Forum Summary

There is no question that high levels of alcohol consumption during pregnancy can lead to severe adverse effects on the fetus, with the most serious condition known as fetal alcohol syndrome (FAS). Many studies have also related alcohol intake during pregnancy with premature birth, low birth weight, and the infant being small for gestational age (SGA).  Data are not as clear on the effects just of occasional or light drinking, but most studies have not detected adverse effects.

The present paper, based on a pooled sample of almost 200,000 women from nine European cohorts, provides data indicating that premature birth, an infant being small for gestational age (SGA), or being of low birth weight do not appear to be associated with light-to-moderate intake (up to 6 drinks/week); these results are similar to those from many other recent studies. In this large study, mothers who consumed greater amounts of alcohol tended to have an increased risk of the infant being SGA or with low birth weight, but such a level of drinking had no effect on the risk of premature delivery.  This cohort consisted almost exclusively of light drinkers; no data were available on other potentially harmful effects of excessive drinking.

An interesting additional finding was that the reported frequency of any alcohol consumption during pregnancy in the cohorts studied has decreased dramatically in recent decades (from approximately 50% of women studied prior to 2000, to 39% in 2000-2004, to 14% in 2005-2011). This suggests that most women are responding to guidelines recommending that a woman not drink during pregnancy.

Based on currently available information, the Forum considers that a recommendation to “avoid alcohol during pregnancy” is appropriate as part of drinking guidelines for the public. However, scientific data, including the present paper, do not suggest that women who may have an occasional drink or very light alcohol consumption during pregnancy should have undue concern about having a premature birth or a low-birth-weight infant.

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 Comments on this critique by the International Scientific Forum on Alcohol Research were provided by the following members:

Mladen Boban, MD, PhD, Professor and Head of the Department of Pharmacology, University of Split School of Medicine, Croatia

Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy

R. Curtis Ellison, MD, Professor of Medicine, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA

Ramon Estruch, MD, PhD, Hospital Clinic, IDIBAPS, Associate Professor of Medicine, University of Barcelona, Spain

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, University of Arizona School of Medicine, Tucson, AZ, USA

Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark

Creina Stockley, PhD, MSc Clinical Pharmacology, MBA; Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia

Pierre-Louis Teissedre, PhD, Faculty of Oenology–ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France

David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa

Andrew L. Waterhouse, PhD, Department of Viticulture and Enology, University of California, Davis, USA

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