No Safe Level of Alcohol Use in Pregnancy

Megan Brooks

January 19, 2012

January 19, 2012 — With respect to alcohol-related birth defects and growth deficiencies, there is no safe amount of alcohol use during pregnancy, confirms a new study based on prospectively collected data on nearly 1,000 women.

"These new findings can help the clinician quantify the importance of discontinuing alcohol as early as possible," Haruna Sawada Feldman, PhD, MPH, of the Department of Pediatrics, University of California, San Diego, La Jolla, told Medscape Medical News.

Dr. Haruna Feldman

"Women who are of childbearing age and who are contemplating or at risk for becoming pregnant should be encouraged to avoid drinking, and women who are pregnant should abstain from alcohol throughout pregnancy," she advised.

The study was published online January 17 in Alcoholism: Clinical & Experimental Research.

Research Challenge

Classic physical features of fetal alcohol syndrome (FAS) include smooth philtrum, thin vermillion border, short palpebral fissures, microcephaly, and weight and height growth deficiencies. Yet, there is a lack of clear-cut information on the risk of each of these specific features in relation to the amount and timing of alcohol consumption in pregnancy.

Dr. Feldman and colleagues quantified risks for these specific alcohol-related features on the basis of specific patterns and timing of exposure during pregnancy. The analysis focused on 992 women and their infants. The mean age of the women was 31 years.

The study was designed to address two challenges in FAS research, Dr. Feldman explained. The first is obtaining accurate alcohol exposure history from the women, which may involve social stigma and recall bias.

"This study helped to improve the quality of that information by collecting information during pregnancy when women were as yet unaware of the pregnancy outcome. The data were also collected by trained counseling specialists who built rapport with the woman and guaranteed confidentiality while collecting sensitive information," Dr. Feldman said.

The second challenge is getting quality information on physical features of FAS. "These cardinal alcohol-related features are often subtle, and a non-expert examiner may miss or misclassify features, and/or can be biased by subjectivity, especially if he/she suspects or knows about prenatal alcohol exposure," Dr. Feldman noted.

"This study used an exposure-blinded expert dysmorphologist to look for these features. Importantly, potential bias due to subjectivity was reduced because these examinations were conducted in the context of a larger study in which women were enrolled with exposure to one of over 70 agents of interest, only one of which was alcohol," she explained.

Patterns of drinking were evaluated by drinks per day, number of binge episodes, and maximum number of drinks. Timing of exposure was evaluated 0 to 6 weeks postconception, 6 to 12 weeks postconception, first trimester, second trimester, and third trimester.

Higher Exposure, Increased Risk

In each pattern the team investigated, higher prenatal alcohol exposure was significantly associated with an increased risk of having an infant born with reduced birth length or weight or having a smooth philtrum or thin vermillion border or microcephaly.

For women consuming 1 or more drinks daily on average in the first trimester, compared with those consuming less, there was evidence of higher risk with higher dose for these outcomes. But there was also "clear evidence that these outcomes did not occur exclusively" at higher doses, the authors say.

The most significant associations were seen during the second half of the first trimester; for every 1 drink increase in the average number of drinks consumed daily, there was a 25% increased risk for smooth philtrum (risk ratio [RR],1.25; 95% confidence interval [CI], 1.14 - 1.36); a 22% increased risk for thin vermillion border (RR, 1.22; 95% CI, 1.09 - 1.35); a 12% increased risk for microcephaly (RR, 1.12; 95% CI, 1.02 - 1.22); a 16% increased risk for reduced birth weight (RR, 1.16; 95% CI, 1.07 - 1.27); and an 18% increased risk for reduced birth length (RR, 1.18; 95% CI, 1.08 - 1.29).

These associations were linear, and there was no evidence of a threshold, the authors say.

Dr. Feldman and colleagues emphasize in their report that the apparent lack of strong associations for drinking during the first half of the first trimester should not be interpreted to mean that alcohol consumption during this period is somehow safe.

"Due to the study design, we were only able to include women who gave birth to live infants," she explained in a statement. "Therefore, we did not include women who may have had miscarriages or stillbirths. It is important to know that alcohol-exposed infants who would have exhibited alcohol-related minor malformations might also be more likely to be lost to miscarriage following exposure during the first six-week window," Dr. Feldman said.

"Important" Study

This is a "very important" and well-performed study, Arne Svilaas, MD, PhD, from Oslo University Hospital, Norway, who was not involved in the study, commented in an email to Medscape Medical News.

Lynn Gretkowski, MD, of Stanford University in California, who was also not involved in the study, noted that "the period of embryotoxicity based on timing and amounts (of alcohol) doesn't come as a surprise, even for prescribed medicines in the first trimester. Insults certainly can be lethal at this gestational age," she said.

Dr. Svilaas and Dr. Gretkowski are members of the International Scientific Forum on Alcohol Research, a joint undertaking of the Institute on Lifestyle & Health of Boston University School of Medicine in Massachusetts and Alcohol in Moderation (AIM) of the United Kingdom. Forum members are not paid; members are researchers who share their knowledge and expertise and put recent research into context with other studies.

Research on the effect of prenatal alcohol exposure has been mixed. One of the more recent studies published in 2010 in Pediatrics and reported by Medscape Medical News at that time found no link between low and moderate alcohol consumption during pregnancy and alcohol-related birth defects. There was, however, a significantly increased risk for birth defects with heavy prenatal alcohol exposure, as expected.

Dr. Feldman's team says it should be noted that their study focused only on alcohol-related physical features. Far more children with prenatal exposure to alcohol may be affected neurobehaviorally, the authors note.

"Future studies should address these same questions regarding gestational timing and dose relative to neurobehavioral outcomes," they advise.

The authors of the study, Dr. Svilaas, and Dr. Gretkowski have disclosed no relevant financial relationships.

Alcohol Clin Exp Res. Published online January 17, 2012. Abstract

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