Pregnant? Still drinking that pot of coffee?

As all y’all know by now, I’m an experienced caffeine junkie. Currently, I’m trying to forgo it again (this Diet Coke right here is merely an aberration, do not look at the caffeine behind the curtain…). But really, it’s everywhere around us. Somehow I don’t think it was QUITE so prevalent until the age of Starbucks. but it seems like now you can’t go anywhere without running into a coffee shop or three. In some cities there is literally one on every street corner. And with the crazy lives we all appear to be living these days, shouldn’t we take whatever legal cognitive enhancement we can get our hands on?
And heck, with a Starbucks on every streetcorner, what’s a poor lady who is…*ahem*…increasing (for those not familiar with the Victorian term, it means preggers), to do? Some of us spend our lives pretty well addicted, but when a women in the US finds out she is pregnant, she is immediately to drop to no more than one caffeinated beverage a day. And 70% of expectant mothers apparently don’t even do that. So the big question is: is our children caffeinated?
ResearchBlogging.org Bjorklund et al. “Perinatal Caffeine, Acting on Maternal Adenosine A1 Receptors, Causes Long-Lasting Behavioral Changes in Mouse Offspring” PLoS ONE, 2008.


As a matter of interest, it turns out that people in most of the world consume about 76 mg of caffeine per person per day. In Finland and Sweden, for some reason, that number is more like 400 mg of caffeine. Any reason why? And I would be curious to know the rates for professors and grad students. I bet they’re closer to Finland.
I’m sure that many of you who have been pregnant have probably been told at some point that caffeine is not good for the baby. High caffeine intake has been associated with bad outcomes, and caffeine has been inplicated as a teratogen (a ‘teratogen’ is something that causes a birth defect). Of course since caffeine has been around for a while, lots of studies have been done, but often researchers use pretty high doses (more than 50 mg/kg, which is even higher than you’d see in Finland). So these researchers wanted to look at effects of lower doses of caffeine, and use a model that was a bit closer to the use you see “on the street”. So they took pregnant mice, and put the caffeine in their drinking water.

A note on caffeine:
Caffeine is stimulant, but it’s not a psychostimulant like cocaine or Ritalin. Instead, caffeine acts as an antagonist at adenosine receptors. Adenosine is a nucleoside (which means that it has a molecule of adenine, like in DNA, with a sugar clinging on), and is generally an inhibitory neurotransmitter, which may be important in promoting sleep. Caffeine antagonizes, or inhibits the actions of adenosine, resulting in less promotion of sleep, and thus more wakefulness. So unlike cocaine, caffeine has no direct effects on the dopamine system (a system important in reward, and a system found to be in common with drugs that are abused). But don’t rule out those indirect effects. It turns out that caffeine has secondary effects on dopamine, because the adenosine and dopamine systems interact. So caffeine intake can produce small increases in dopamine (Fredholm, 1999). This is the first I’d heard of it, and I think I’m going to have to investigate.
Caffeine, like many drugs, has what we pharm people like to call a “biphasic effect”. At lower doses of caffeine (50-300mg, about what you’d get in 1-3 cups of coffee), caffeine acts as a stimulant, perking you up, and apparently giving you enhanced ability to concentrate and a feeling of well being (due to the dopaminergic interactions, apparently). At higher doses (300-800 mg, when you drink the whole pot of coffee) caffeine can make you nervous, shaky, and unable to sleep. When studying this in lab animals, you can’t really ask them about feelings of well-being or nerves, but it turns out that caffeine makes a good motor stimulant (like cocaine) at lower doses, while higher doses can induce things like seizures and stereotypies.
I should point out that caffeine doesn’t come close to cocaine in terms of addictive potential, though. First of all, it’s a lot less potent. “Low” doses of caffeine in rats would be something like 25 mg/kg, which, if you gave that dose of cocaine, would send the rat through the roof. So caffeine is a lot less potent. Secondly, the dopaminergic actions of caffeine are secondary to the adenosine reactions, and dopamine increases are much lower than anything you’d ever see with cocaine, even at the highest doses.
Ok, that was a bit of a long aside. But now you know.
Anyway, we’ve been testing the effects of drugs given to the mother on the babies for many many years, and it’s basically assumed that, if there are effects in the fetus, it’s due to the drug crossing the placenta and affecting the fetus itself. What’s crazy about this article is that they imply that it might be the effects of caffeine on the MOTHER influencing behavioral outcomes in the babies. And here’s how they did it.
They put caffeine in the drinking water of pregnant mice, titrating the dose to about the equivalent of 3-4 cups of coffee a day. Of course they had a group of pregnant mice that didn’t receive caffeine. They then took the OFFSPRING of those mice and ran them in locomotor activity tests (basically, put a mouse in a box. See how much it runs. Yay, you have data). It turns out that caffeine treated pups ran around a lot more than pups with no caffeine. Not only that, but when tested with cocaine, the caffeine treated pups proved more sensitive to the drug than the uncaffeinated pups (I have some small issue with that, but I’ll address that in the comments).
So they they looked at a new set of mice. These mice had been genetically altered to display low adenosine receptors, like someone would after prolonged exposure to caffeine (in other words, tolerance). These adenosine knockdown mice ALSO produced pups that were sensitized to caffeine and cocaine, just like the pups of mothers given caffeine. From this, the authors said that these sensitizing effects were due to the effects of caffeine on the mother, NOT the direct effects of caffeine on the pups.
And it gets better! They tested the GRANDCHILDREN of the caffeine treated mice, and found that they were also sensitized. Apparently this thing is all in the family.
Comments:
1) I really like the study over all, but I wonder about the effects that they got when they did a locomotor test following cocaine. I have given a LOT of cocaine to a lot of mice, and while their cocaine reaction in the caffeine treated mice looks good, the non-caffeinated mice barely show a blip. At 10 mg/kg cocaine (I assume it was given i.p., but I could be wrong), they should be seeing a nice significant increase in locomotor activity. Makes me wonder what their saline injection looked like.
2) Although the A1 knockdown mice (the ones with low levels of Adenosine receptors, like they had been drinking caffeine) produced pups that were sensitized like caffeinated pups, I’m not sure that this means that the mother’s adenosine receptor levels were to blame, even regardless of the genotypes of the pups. We know that adenosine has dopamine system interactions, and it could have been differential levels of dopamine, or another neurotransmitter affected by adenosine, that caused the changes. Furthermore, knockdown mice like these are born and raised this way, so you have to account for the effects of growing up with reduced adenosine receptors. So I think they might want to do adult knockdowns before they make a sweeping conclusion like this.
In general, I think this is a really neat study, though it’s certainly made me glad I’m drinking less caffeine than the Fins now. This has some pretty sweeping implications for things like hyperactivity in children, but I wouldn’t get all up in arms yet. Of course these are mice, not humans, and changes in adenosine receptors artifically could have difference consequences in humans than in mice. More investigation is obviously needed. But for you ladies out there who have one in the oven, you might want to pass up that diet coke. It might save you being a little frazzled by that locomotor stimulated child later.
Olga Björklund, Johan Kahlström, Peter Salmi, Bertil B. Fredholm (2008). Perinatal Caffeine, Acting on Maternal Adenosine A1 Receptors, Causes Long-Lasting Behavioral Changes in Mouse Offspring PLoS ONE, 3 (12) DOI: 10.1371/journal.pone.0003977

21 Responses

  1. I drink a lot of coffee. I used to drink a lot MORE coffee than I do now, and I didn’t significantly drop when I was pregnant with my first, although I went completely off it went I was pregnant with my second. I also drink tea, and did with both pregnancies.
    My friends have joked (for years now) that my caffeine intake affected my first child. Makes you wonder. Ah well, bit late for me to personally worry about it now. Interesting article though.
    PS: In the UK you’re advised to have no more than four caffeine-containing drinks per day, including tea. At least, that was the advice three years ago.

  2. “In Finland and Sweden, for some reason, that number is more like 400 mg of caffeine. Any reason why?”
    That’s simple. We drink more coffee, because our coffee is the best in the world.
    Any more questions?

  3. Wait a second… grandparents?
    So even if *I* don’t drink any coffee, I’ll still have hyperactive little sprogies because of how much my mom had?
    Not fair, god. Not fair.

  4. Both times I was pregnant I suddenly found coffee disgusting. I resumed drinking coffee (not much of it) after the first trimester.
    BTW, is there any evidence-based reason to drink zero alcohol (as opposed to, say, 4oz of wine twice a week) during pregnancy? It seems medical advice on different sides of the Atlantic Ocean is inconsistent about this.

  5. I’m sure my mother drank many, many cups of coffee while pregnant with me. She never smoked cigarettes and was never big on drinking alcohol, but she and my father always had the coffeepot fired up. And I’ve absolutely loved caffeine since I was old enough to steal my mom’s coffee cup and toddle away with it.
    The funny thing is that I have always had quite a high tolerance for its effects. I can’t even detect the effects of caffeine from cola unless I drink lots of it. Then again, I tend to be like that with most medications, even when taking them for the first time. My body must be very hyper about metabolizing these things.
    As for Mom: She’s finally given up coffee at age 89. Not because of the caffeine, but because her doctors restricted her fluid intake after she had a very nasty episode of hyponatremia.

  6. And heck, with a Starbucks on every streetcorner, what’s a poor lady who is…*ahem*…increasing (for those not familiar with the Victorian term, it means preggers), to do?

    um…are congratulations in order?

  7. arvind: oh, YIKES NO! But I suppose the way I wrote that is a little ambiguous…my eggo is not preggo.
    Lassi: I don’t know…the middle east makes some GOOD coffee. As does Europe. Do you have data? Or do you want to send me a sample? 🙂

  8. Please, a little common sense: if you are *ahem*, “increasing,” would it not make sense to cut back to one small cup a day (morning or evening)? And if you must have a second, could that not take the form of a cup of tea instead?
    Just cutting back, on many things, makes sense for pregnant women. Is a lot of sugar good for the baby? No. Should you cut out all sugar intake – probably not. Is alcohol good for baby – no. Is like one glass of wine on a few special occasions during the entire pregnancy tolerable? Yes.
    I have a similar experience to Julie’s, above. My Mom was a coffee drinker, no one was around to tell her not to when she was pregnant. My physical response to stimulants is similar to what she describes.

  9. Pregnant? No actually, I’m not. Why on Earth would you imagine I was? Does my stomach really stick out that far?!

  10. I’m with you 100% on your first comment, Sci. I too have some experience in this field, and to see no effect of 10 mg/kg coc in C57Bl/6 mice is totally weird! To be fair, I’ve never given that dose to 2-month-old female mice, but still…
    I’m thinking the stress of the injection is perhaps to blame for the weak water group response. If they didn’t give sham (saline) injections to the mice prior to cocaine (and it looks like they didn’t), I wouldn’t be surprised if injection stress decreased the locomotor activity of the 10 mg/kg coc mice. Likewise, I’m sure the locomotor activity for the saline controls was poor if the mice weren’t acclimated to receiving i.p. injections. Even if mice are well-handled, the first time they’re injected with anything is stressful, which would decrease locomotor activity.
    Now what’s weird is why maternal caffeine exposure would protect against this. Perhaps they’re arguing that the caffeine mice are sensitized? And also, couldn’t it be argued that the caffeine mice are actually in caffeine withdrawal?

  11. Sorry, my comment is a little unclear, as it implies saline controls exist. There are no saline controls in Fig. 2. The ones I mention are hypothetical, since Sci mentioned she would like to see some data from saline control mice. I was guessing what I think those data would look like.

  12. Mousegirl: see, in my experience, giving a saline injection to a non-handled mouse results in augmentations in locomotor activity due to the stress, not less loco. And they were working with habituated mice, which is where it gets really weird. They really should have seen something. I’ve injected two-month only mice before (and even younger than that, 2-months is the adulthood cutoff generally), and 10 mg/kg cocaine never fails. =

  13. Okay, maybe I missed something. But if the offspring were MORE sensitive to effects of caffeine later on, couldn’t it logically follow that they might be LESS likely to intake a lot of caffeine? I guess in my head it just seems that if a small amount of caffeine does the trick, why would you want more? I know a lot of people who are really sensitive to caffeine so they only drink it in small amounts.
    And from my generation backward, pregnant moms did absolutely jack shit differently when they got pregnant unless something made them feel ill. My mom smoked, probably drank (though not a lot), and certainly didn’t cut back on her coffee intake. And I’m fine. (Well, I suppose that’s debatable….)
    What I’m really, really curious about is the allergy “epidemic” among children born in the last 10 years or so. When I was in school, there would be maybe one person who was lactose intolerant (and we all thought it was weird), a couple people allergic to bee stings, one or two allergic to shellfish. Nowadays, if you so much as EAT a peanut butter cracker while LOOKING at the “allergy-free” table in the cafeteria you have committed a severe security breach.
    Now they tell mothers to stay away from nuts while pregnant, lest it induce an allergy once the child is born. But seriously, is someone telling me that in the mid-90’s, a bunch of pregnant women went on a Planter’s binge???

  14. And this is why behavior is so crazy! Our lab has consistently seen decreased locomotor activity as a response to injection stress in mice approximately that age, C57Bl/6 background. Decreased horizontal beam breaks, center time, the works. We do saline injections to habituate our mice to the injection procedure before all our behavioral experiments.

  15. We do the same, but for the opposite reason.🙂 Go figure. But as long as everyone’s habituating, we’re good to go. I HATE papers where I see studies of activity in unhabituated mice. Shows they clearly haven’t been using mice for very long.

  16. I hate that too!!
    And sorry for hogging all the comment space.🙂

  17. “I have given a LOT of cocaine to a lot of mice…”
    And they said Hunter S. Thompson was dead.

  18. Hunter S. Thompson would have kept all the cocaine for his ownself.🙂

  19. Coffee is a major component of social interaction is Sweden and Finland. You get to know new people by talking together over cups of coffee. You’re expected to treat guests or visitors to coffee (that goes for companies and schools, not just homes) and the visitors are expected to agree. You have nary a meeting or any kind of social gathering that does not involve mugs of coffee on the table, and many workplaces still have formal coffee breaks morning and afternoon. At university it’s quite common to see both students and the teacher with mugs of coffee during the lectures.
    When it’s available and socially acceptable almost everywhere and everytime, consumption goes up.

  20. The life of a mouse – drink coffee, have sex, have the pups taken away after birth. Rinse, repeat. Not too shabby.
    I’m with Julie and yogi – caffeine in pop just doesn’t seem to be there. (I never toddled away with the coffee, but I know it was always there when I was growing up.) The fact that I can now use this as an excuse not to present the parents with grandchildren is a wonderful side effect!

  21. Do you dose your mice in the light or dark cycle, scicurious? If I’m reading this article correctly they did the locomotor assay in the light cycle.

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