Contra Oster on Alcohol in Pregnancy. Part 1. The pharmacokinetics of alcohol metabolism

This is the first of a series on how Oster is wrong on drinking in pregnancy in her 2013 book Expecting Better: Why the Conventional Pregnancy Wisdom is Wrong and What You Really Need to Know. For this part, we'll focus on how and why her biological model of ethanol metabolism is incorrect. This premise forms part of her argument on why it's acceptable to drink 1-2 drinks* a week in the first trimester and more later in pregnancy. Oster writes, To understand why there is a difference between excessive drinking and moderate or light drinking, it's useful to think a little bit about how the biology works. Many women seem to think that when they drink, that glass of wine is channeled directly to the fetus. People correctly note that you would not give your infant a glass of wine, so why would you give your fetus one? Needless to say, this is not really how it works. When you drink, alcohol enters your digestive system and is passed into your bloodstream. Your liver processes the alcohol into a chemical called acetaldehyde and then into acetate. The acetaldehyde is toxic to other cells, and depending on how quickly you drink, it can remain in your bloodstream. You share your blood with your baby through the placenta; acetaldehyde, which remains in your bloodstream, is therefore shared with the fetus. Your baby actually can process some alcohol, but not as much as an adult (obviously). If too much acetaldehyde is passed to the baby, it can get into his tissues and impact development. When you drink slowly, you metabolize much of the alcohol before it would get to the fetus. If you drink quickly, your liver cannot keep up and toxins are passed to the fetus. This is why binge drinking is so bad, but it also illustrates why negative effects of light drinking do not follow directly from negative effects of heavy drinking. The bolded statement is, quite simply, not in any way true when it comes to alcoholic drinks, and particularly not in the first trimester. You do not meaningfully metabolise 1 drink before it makes it to the fetus. We know this because your blood alcohol level rises; blood alcohol is a measure of how much ethanol is actually in the blood. Its very presence in the blood means it hasn't been metabolised yet and is free to diffuse into fetal tissue. Oster is completely correct that a woman drinking 1 glass of wine isn't like a fetus drinking 1 glass of wine itself. For one, body size! A first trimester embryo/fetus has less mass than the mass of the ethanol in the wine itself so this is trivially true. We also have enzymes in our intestinal tract (ADH4) that digest some of the ethanol before it reaches the blood stream. However, these only digest a very small fraction of the ethanol we consume. The vast majority (92-98%) is metabolised by blood passing through the liver. To drink so slowly that no alcohol makes it into the maternal blood stream? I cannot provide an exact estimate on how little ethanol or how slowly that would be because no one has bothered to study such tiny amounts of consumption. I found one study where they had volunteers drink one beer very slowly - over 2 hours vs 1 hour or half hour. Peak BAC was only reduced for the 2 hour group but the fall in BAC was also slower because consumption of 20ml/5min still grossly outpaced ethanol metabolism. Any biologically plausible ethanol consumption amount that could show no rise in BAC would be necessarily have to be much, much less than one beer over two hours and probably in the "trace amounts" category. We can discard this idea entirely unless Oster imagines women are drinking their one glass of wine in 100 μL aliquots over a time scale of days. In a more realistic scenario, after 1 drink, it takes about a half hour for maternal BAC to peak - during that 30 minutes, that ethanol is continuously diffusing into both maternal and fetal tissue. In the first trimester, the placenta is yet to form and so no placental filtering is occurring. The rise in BAC indicates it's being absorbed faster than it's being metabolised; if it was being metabolised faster, it'd be dropping. Some of that ethanol is being metabolised, but that's already calculated in with maternal BAC - if it hadn't been, BAC would be even higher. So it's not enough to counteract the rise in BAC. But let's continue on with her explanation; Oster claims maternal acetaldehyde, a metabolite of ethanol, gets "passed to the baby" (this is almost certainly false but we'll entertain it). How much alcohol, exactly, can you metabolise into acetaldehyde, and how quickly? If acetaldehyde getting passed to the baby is the problem, we need to calculate at what threshold it will build up. Let's calculate! Steel-manning the maternal acetaldehyde hypothesis One standard drink (in the US, that is) is defined as containing 14 grams of alcohol. This is actually a lot of alcohol! The liver does this pretty slowly. For the average metaboliser, hepatic enzyme is saturated at 15–20 mg/100 mL, w