Thursday, October 7, 2010

The chaff for the grain: the effects of alcohol during pregnancy

A study just published in the Journal of Epidemiology and Community Health reports that light drinking during pregnancy does no harm to the child.  That is, children of mothers who were 'light drinkers' during pregnancy had no increased risk of 'socioemotional problems and cognitive deficits at age 5'.  This is a follow-up of a study that showed no risk of light drinking to three year olds in the same sample.

The story on the BBC website says:
Drinking one or two units of alcohol a week during pregnancy does not raise the risk of developmental problems in the child, a study has suggested.
Official advice remains that women abstain completely during pregnancy.
A study of more than 11,000 five-year-olds published in the Journal of Epidemiology and Community Health found no evidence of harm.
There were more behavioural and emotional problems among the children of heavy-drinking women.
Mothers were first interviewed when their infant was 9 months of age (sweep 1).
Questions were asked about mothers' drinking during pregnancy, other health-related behaviours, socioeconomic circumstances and household composition. Sweeps two and three of the survey took place when cohort members were aged approximately 3 and 5 years. At the age 5 years home visit cognitive assessments were carried out by trained interviewers and questions were asked about the cohort members' social and emotional behaviour, socioeconomic factors and the psychosocial environment of the family. 
Now, this raises a number of alarm bells for anyone used to thinking about study design issues.  For one, sensitive subjects are hard to measure accurately, especially by recall interviews.  Sexual behavior, alcohol consumption, and so on are notorious for that problem.    Doctors, for example, routinely double the number their patients give them when they're asked how many drinks they consume per day. And alcohol consumption during pregnancy is particularly sensitive. So whether or not the data are reliable in this study, especially given that it was recall data -- mothers were asked to remember how many drinks they had per week during each trimester of their pregnancy when their infant was already 9 months old -- is one possible problem here.

But perhaps that's not the most important issue here.  Confounding is an important potential study killer any time, but  this study seem particularly fraught.  The authors do recognize that confounding variables could be a problem, that many other factors could influence socioemotional behavior, not just alcohol consumption during pregnancy, and they try to control for some of these.  But, given how many different things can affect a child's behavior between pregnancy and age 5 (that is, in fact, everything), it's very hard for us to believe, no matter how well possible confounders are controlled for, that it's possible -- or even sensible -- to try to boil down the explanation for behavior differences between 5 year olds to the difference between 3 and 5 drinks a week.  Especially given the fragility of the data on alcohol consumption. And the idea has been prevalent that alcohol can pose a fetal danger even so early that the mother doesn't yet realize she's pregnant; so if she quits or cuts back when she does learn, reliance on recall may lose some accuracy.

That said, let's turn to the results.  Here's the link (if you can get access) to the table that interests us most, the prevalence of socioemotional problems according to whether the mother never drank, didn't drink during pregnancy, was a light, moderate or heavy drinker.  Note that in every problem category -- every category -- the prevalence of the problem under study (conduct problems, hyperactivity, emotional problems, etc.), and the odds ratio, are higher in children of mothers who never drank than in either all children, or all children except for those whose mothers drank heavily during pregnancy.  That's in all the models they tested, from controlling for just one variable, age of child, to controlling for many different variables. Not drinking is a stronger risk factor than almost any amount of alcohol.

Interestingly, and curiously, the authors use not-in-pregnancy as their reference, rather than not drinking at all.  Clearly they can be missing some sociocultural or other environmental confounders by doing that.  Also, the data are reported in terms of 5% significance, with little if any mention of the correction for the huge number of tests they have done.  They did find some sorts of trends, which mollifies this concern, but only somewhat.  They report this as a confirmation of earlier findings, but that, too, is a bit uncalled for since this is an extension of, and hence not independent from, the earlier phases of the same study (it includes the earlier results, essentially).

When there are huge numbers of covariates, and potential confounders, and clearly countless other factors could, in principle, be unmeasured confounders, one has to be circumspect about this study.  Even if the results are correct as reported and interpreted, the net impact of moderate drinking only applies after regressing out the other measured factors.  They may, in aggregate, have a much greater effect on childhood behavior risks than the net effect of pregnancy-imbibing, so that the absolute effect of drinking (even if alcohol is the actual cause itself) is going to be small.

If we can believe the data, and that never drinkers really never drank and so on, this certainly makes one wonder about the effects of unmeasured confounding variables, and raises the question of how much of the reported effect due to heavy drinking really is due to alcohol.

And yet again, about publishing obviously inconclusive studies....  Such studies are very costly, and likely to change years hence as envirionmental exposures and confounders and ways of measuring things change.  It is not a shock to learn that a touch of a drink now and again is not a particular problem, especially if it relaxes the mother, say.  The most important question is not that, but whether very early drinking can lead to birth defects of various sorts.  The reason is that the very early embryo is only a few cells with most of its differentiation yet to come, so a damage to any cell can have proliferative effects.

But later, during the period of organogenesis and then mainly growth, fetuses are generally much more robust to small external exposure effects. There are many more problems about pregnancy and child health than the rather trivial effects that this very large study, even if all its results are true, deals with.  And the solution to many of the real problems is:  moderation, improvement in socioeconomic differences.  But those are deeper problems that society doesn't want to deal with.  It's safer to look at a blizzard of statistical data and talk, with serious demeanor, about the minor things that might be guessed at and perhaps even changed.


Holly Dunsworth said...

Thanks Anne.
Wishing so many studies on human health and behavior weren't based on self-reporting. Then again, we often wish nonhuman animals could talk to us so we could study them better.

Anne Buchanan said...

Yes, and self-reporting is only one of the problems with this study. Alas.

If nonhuman animals talked to us, we'd just have to wonder what they really meant....

Holly Dunsworth said...

Science reporting is AWESOME for those who have journal access - It alerts them to the new study and is often entertaining and thought-provoking but all that comes with knowing that the news report won't be the end-all be-all. If you have access you can just read the original article to follow-up.

But for the majority of people without journal access, science reporting can read like movie reviews for movies that only the critics and the people in the movie biz get to watch.

Ken Weiss said...

The problem is complex causation in complex societies. An industry, like epidemiology or genetics, has to keep the factory running so we get a continual flow of superficial studies.

At the same time, if we identify real problems, as opposed to largely invented ones (as in this case, perhaps, because so many other things than a drop of the nectar cause childhood problems), then it is not clear what other approaches than total Big Brother monitoring everything everybody does, can get convincing answers.

And it's worse, much worse than that. First, because these middle-class overkill studies deal with trivial problems like this one, rather than the more expensive, serious problems of SES-based disease and quality of life risks.

And second, there is the Heisenberg uncertainty effect, that measuring something changes it so it can't be fully understood: As soon as such a study is reported, lots of people change their behavior. In the past, women went on the wagon if they even _might_ get pregnant--probably over-worrying and turning into bores for their spouses. And now the light tipplers will grab their spouses and hustle them into the bedroom for a tumble.

And remembering these changes years later, which are ephemeral because they'll change again with the next science news report, means that the causal landscape is affected by the studies themselves.

A difficult tangle for a serious-minded epidemiologist to deal with.

Anonymous said...

The BBC story is dangerous. They clearly don't know what they are talking about.

One of the most pitiful results of alcohol is the Fetal Alcohol Syndrome. Alcohol can reach the fetus and abstain it from sufficient oxygen and nutrients. This can happen due to regular drinking or after a one time excess during pregnancy. Children with the syndrome often have malformations in the face are educationally subnormal or suffer from Attention Deficit Disorder (ADD).

Let them read my post called "Alcoholic beverages, maybe not a good idea"

Texbrit said...

Woo-hoo! They can now have 1-2 tiny glasses of wine per week? Par-teee!

Sarick Rochette said...

Sarah & I were talking about this study the other day, and she absolutely went livid when we got to the segment about this being "definitive" proof that low alcohol consumption during pregnancy is not detrimental to cognitive ability.

Sarah a school psychologist, so this issue is particularly important for her. Her point was that cognitive difficulties and intellectual deficits caused by fetal alcohol syndrome or from fetal alcohol effects won't necessarily manifest or solidify by age 5. So it is meaningless in many ways to say that by age 5, these children show no negative impacts from their mothers' alcohol consumption during pregnancy. You simply can't measure any effects yet.

I hope that I haven't totally mis-characterized her arguments, but she's got a point. Reporting these results now makes sense for getting further grants, but it is not at all clear that these children won't show signs once the IQ measures typically used for small children stabilize - typically after age 7.

And then there is the question of what IQ actually measures...

Ken Weiss said...

The cynical side of this is the way investigators use endless studies to keep the funds flowing, releasing 'update' reports periodically. I know of no study of this type that has voluntarily said it's time to close shop, nor none of any size that the funders had the guts to terminate because it had done its job.

In t his case, there is the Heisenberg factor that means that even if later-childhood effects do arise, the number and nature of causal factors will increase also (say, trauma in school at age 6 affecting behavior at age 8), so the same size study will be decreasingly powerful relative to the number of variables it should take into account.

Further, as risk factor exposures change, since all these things are contingent and interactive, the risk estimates for this cohort, related to the past 20 years of history, won't apply to the future with knowable precision.

Meanwhile, what else could the funds be used for, that would have more important benefit?