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Payment of $45 for three month plan $15 per month equivalent required. New customer offer first three months only, then full price plan options available, taxes and fees extra. See mintmobile.com Vitamin D is a fat soluble vitamin that's obtained largely from consuming fortified milk or juice. It's in fat, fish oils and of course, as we're talking about here, dietary supplements now. It is produced in the body. It's an endogenous vitamin. It's produced in the skin with exposure to, as we said in the intro, sunlight. Vitamin D that is ingested or produced in the skin has to undergo hydroxylation to have some kind of activity. And there's two hydroxylations that are necessary. The first hydroxylation is in the liver. That's where we get 25oHD. The that is 25 hydroxy vitamin D. That is the thing that we should be measuring either before pregnancy, ideally as either a well woman check or a preconception consult or if you want to in pregnancies to see where they're at. That's fine and we'll get into that in a minute. But that's the one that we checked 25 hydroxy D or 25 OHD and I'll tell you what a low level is in just a minute. However, once you get 25oHD in the body, it needs another hydroxyl Group and added to it. And that happens in the kidney. That is 1 comma, 25 dihydroxy vitamin D, and that's the one that is physiologically active. All right, so you get vitamin D kind of produced in the skin, or you take it by mouth, goes into the liver, liver hooks on an OH group, then goes to the kidney there, hooks on to another OH group. So you get two of them,125 dihydroxy vitamin D. But the one that is measurable in this serum where we actually say you're adequate or not adequate is maternal serum 25 hydroxy vitamin D. So 25 oh D. Okay, now if somebody is found to be deficient in that level, let me just say right now, even though it's controversial, what, what is considered a low level in different guidances, different societies say different things. For the US Most people use a level, a value of at least two 20 nonograms per milliliter. Now, when we report vitamin D serum levels, some use nanomoles per liter, but the majority use NG per ML. That's what we're going to be talking about here. All right, so nanograms per milliliter. It's at least 20 at that level. So if somebody is 20 nanograms per milliliter or less, then it's considered generally safe to take like 1,000 to 2,000 international units or IUs per per day of vitamin D. Okay, so 1,000 to 2,000 vitamin D seems to be what's recommended for the US now out of ACOG's committee opinion number 495. Remember, this was originally out in 2011 and then reaffirmed in 2024. It's very brief and it does say, look, we know that there are some, some potential issues here not just for bone metabolism, overall growth. There is things with, with child development. There is issues of like, if it's severely low and also part of low calcium. I mean, there could be disordered skeletal formation or homeostasis in the child. You can get congenital rickets and even fractures in the newborn. But in general, you know, the data is pretty controversial. We don't really know what, whether it's 20 or should it be maybe 30? So there's a lot of unknowns. And then it says this, quote, recommendations concerning routine vitamin D supplementation during pregnancy beyond that contained in a prenatal vitamin should await the completion of ongoing randomized clinical trials at this time. Here it is, guys. There is insufficient evidence to recommend vitamin D supplementation for the prevention of preterm birth or preeclampsia. End quote. Okay, do we get that? Because this is gonna come back in just a minute to show you how controversial this is. Now, my take is this. Now remember this? Reaffirmed originally out in 2011. Nothing has changed. Reaffirmed just last year in 2024. Insufficient data for preterm birth and preeclampsia. I get that. However. However, here's the devil's advocate. Let me just give the rebuttal and I'm going to lay this out here to show you how controversial this is. And the other data that says, no, that's not right. There is some association. It's not a great association, but there is some association. And then we're going to culminate this discussion with the February 2025American Journal of Clinical Nutrition publication. Okay? So, yeah, and remember, is it. Can it help? Yes. Can it hurt? Can taking extra vitamin D hurt? Probably not. Okay? So as of right now, though, just to be clear, from ACOG's committee opinion, which was reaffirmed last year, now, not enough data. I don't know, you can screen maybe those who are really at high risk, like those who don't get a lot of sun, like in the Pacific Northwest, or as new commentaries have said, everybody. Because nobody's getting the direct amount of sun that we should for adequate vitamin D naturally. Okay? And there's a whole. You talk about controversial. I mean, even to mood disorders and anxiety, Vitamin D has been looked at with the key word being controversial and conflicting. But once again, we know that there's so many things that vitamin D has its hands in. Why not maximize this? Now, remember, this is saying, unsure if supplementation during pregnancy is going to be valuable or not. My take is, again, why not just get back to better homeostasis anyway? But it seems to be what you enter pregnancy with, that vitamin D status and preterm birth, that seems to be the catch. So first of all, when you read an article on vitamin D and preterm birth, the first question you should ask. Well, several questions. The first one, though, is what are we talking about here? How you enter the pregnancy game or what the vitamin D levels become in pregnancy? Okay, so was it okay when you started and then they fall off or were they low to begin with? It seems to be that when they're low to begin with, that seems to be the better association with preterm birth. Everybody. Good. Second is when you read an article on vitamin D in pregnancy, is what level did they use to actually define low? Remember, ACOG and most people in the US use 20 nanograms per milliliter, so that's important. And then number three, did they actually measure what they're supposed to, which is 25 HD? Okay, everybody clear. So we're starting out again, going back in time originally to 2011. Reaffirm, though last year. And then that knocks out. We've already talked about that. That is ACOG's Community Opinion 495. Now, let's walk down this. Okay, so 2011, I know it was reaffirmed last year, but just stick with me here as we build our timeline. It's going to be very fast. Famous last words, 2011. And now let's jump forward five years to May of 2016 in the Journal Nutrients. Okay, Journal Nutrients. This is actually a meta analysis of observational studies. Okay, so the title is, does Maternal Vitamin D Deficiency Increase the Risk of Preterm Birth? Did y' all get this? Now, this is five years, five years after ACOG's bulletin. And the answer is yes, but maybe. Did y' all like that? That is totally the answer, guys, as those of you who are getting ready for potentially fall oral boards. And again, I'm talking about, like, they're like, oh, my God, please don't talk to me about that. I got time to go because we're only in February when we're recording this. Oral boards start in the fall. No, but it's time to think about this now. Time to think about this now. And then you check the box. So if your ass is vitamin D, increased risk of preterm birth. Yes, but maybe. Let me explain. Okay, so this meta analysis of observational studies. Again, I'm just going to do this quickly because I'm building my case here. 2016, showing you the controversy ending, of course, in February 2025. Here it is. Quote, the evidence presented in this article indicates an association between vitamin D deficiency and an increasing risk of preterm birth. End quote. Stop there. All right, so there you go. First sentence at the end of all of the statistics and blah, blah, blah, and all the studies and all of it. And I've looked at it, guys. Trust me. You're like, oh, well, there you go. So the answer is yes. But wait, here it is. Quote, pregnant women with serum vitamin D levels less than 20. There it is. 20 nanograms per milliliter experience an increased risk of preterm birth. Here it is. Here's the but it's complicated part with an odds ratio of 1.29. So let's stop there because I'm gonna give you the confidence interval in a minute because that odds ratio, which is incredibly non impressive, you need the confidence interval to figure that out. So very briefly, remember, and we've talked about this before, and we're not gonna do a mini. But an odds ratio needs to be. To be considered a true. Outside of the realm of maybe confounding technically, two or more like, that's a double of the risk. Anything that's like a 1.2 is like maybe 20% increase. 1.5 is a 50% increase. You get this, right? And so it's higher. Yes, but it still includes one. So the odds ratio has one in the number. So it's 1.1, 1.2. There's an association, but it's not very impressive at all. The confidence interval for this odds ratio of 1.29 according to this 2016 meta analysis was 1.16 to 1.45. Again, still hovering around 1. So to be very clear, yes, it was a higher risk. It was above one. So, yes, it increased the risk, but not by a lot. Do you all get this? That's why it's important to know statistics. This is the exact same thing, guys, that we may talk about in another episode, because I still haven't gotten around to do that. Something that's kind of freaking people out is the use of larks. So progestin only contraception. This just came out. Also February 20th. No, it's January. It was January 2025. That increased the risk of like, breast cancer. That's all we need right now is weird information to freak people out of birth control. Yes, but not so much. So if you take a look at those confidence intervals and those odds ratio, guys, for things like a levonorgestrel releasing system or the etonorgestrel implant, they even threw in Depo Provera for that study. Okay, again, I'm not talking about this, but this was out of the journal of the National Cancer Institute just in January. I think I'm gonna talk about that in a separate episode that freaked people out because they're like, oh, it did increase the risk of breast cancer. Yes, but it was under 1.5, y'. All. And the confidence interval hovered around 1. I'm not worried about. I'm not worried about that. Even in BRCA carriers, guys, that's not a big deal. Okay, so it's the exact same thing here related to vitamin D. Yes, it did increase it, but. But it wasn't really impressive. Now, I'm not going to leave it here. I'm not going to leave it here because there's more that we're going to get to. So. I know what you're saying. Well, wait a minute. You sold this thing like it's a. It's a big association here. I'm not done yet. Remember ACOG? Now we're at 2016 and we're gonna do some more. But as we leave this 2016 publication, let me just read you this quote. More studies are needed to better understand the effect of maternal vitamin D on preterm birth. And well designed trials are required to determine the explicit effects of vitamin D supplementation and prevention of preterm birth. End quote. True. Absolutely right. But again, low risk intervention, potentially some reward. So automatically I'm in. Yes, I'm a big fan of vitamin D supplementation. I think it can definitely do some good. And the chance that it hurts is extremely small to none at all. Okay, so so far I've laid out the ACOG stance that, I don't know, maybe, maybe not. We need more data. It's insufficient data. Not that there's no data on preterm birth, that it's insufficient. We have this one from 2016 that says yes, but the odds ratio is very much. Nah, not great. Now let's get into the 2018. Something from 2018 from SMFM, then we'll take a quick break. All right, Notice getting closer in our timeline to February 2025. Okay, so very quickly, this is SMFM's Do's and Don'ts, which we've covered many times in different, different aspects. But this was out in 2018, so two years after that. Okay, just very quickly talking about vitamin D supplementation as one of the things on the do's and don'ts. Okay, quickly on vitamin D. Oh, my page went away. Well, that sucks. Hold please. Hold please. Hold please. I totally lost where I was at. What happened to my thing? Michael, One second. What? Okay, okay, okay, I got it, I got it. So vitamin D, vitamin D deficiency. Here it is. Quote. Vitamin D deficiency is associated with several adverse outcomes such as preterm birth and preeclampsia. End quote. What did you all get? Remember, this is now through SMFM, published in the Green Journal through ACOG 2018. Vitamin D deficiency is associated with several adverse outcomes like preterm birth and preeclampsia. That's not what ACOG said in 2011 and reaffirmed in 2024. Did y' all get this, guys? This is why we do this episode. These shows, these episodes is to lay out everything together to take a look it on top. Like we're in a drone view looking down to go, well, what's the bulk of this thing say? Because if you just read that, that committee opinion from 2011, reaffirming of 2024, like, oh, okay, not enough evidence. No, no, no, wait a minute, wait a minute. It didn't say not enough. It said insufficient. I'm sorry, it didn't say that there's no evidence. It said that there's not enough, that there is insufficient evidence. And that's different. But, but here's where. Let me continue. I don't want to read you just an excerpt. I want to read you the whole passage here from 2018. Then we'll take a break. Quote, Vitamin D deficiency is associated with several adverse outcomes like preterm birth and preeclampsia, but it is currently unknown whether supplementation improves outcome. End quote. Well, there you go. So it restates again. ACOG stands that it doesn't recommend routine screening unless there's somebody who is known to be deficient or doesn't get sun exposure or has another endocrine issue. And it's unclear if supplementation helps. All right, well, if it doesn't say that supplementation does not help, it says it is unclear. So if it could be clear, if it could be helpful, why not? So there you go. Out of 2018. Vitamin D deficiency is associated with several adverse outcomes such as preterm birth and preeclampsia. Interesting or what? Guys, you see what we're doing here? Building the case. When we come back, we're gonna do two final publications and then we're going to wrap it up. The first one is going to be from Current Opinions in Obstetrics and gynecology from 2020. And then we're going to highlight an SMFM poster presentation from 2023. And then we're going to get into our true none of those. Or actually what we're reviewing. We're reviewing the February 2025 publication. That'll be our last thing to do. So coming back, we got two to help build our case. And then the final article in review. And then we'll call it a day. We'll be right back. Eczema isn't always obvious, but it's real. And so is the relief from Ebglis. After an initial dosing phase, about 4 in 10 people taking EBGLIS achieved itch relief and clear or almost clear skin at 16 weeks. And most of those people maintained skin that's still more clear at one year with monthly dosing.

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Hey, we're glad you're part of our podcast community. You're listening to Clinical Pearls. All right, look guys, I told you I was going to try to stick to my word and try to do this in a more rapid fire way. But sometimes there's just so much to put in there. And look, if I just gave you the 2025 February article, I here's what it said, but don't give you any of the context. That's fine, but that's not how we do it here. I want you to have as much ammunition and evidence based data to make your own opinion. Okay? Like I said, I'm a big fan of Vitamin D. I think, I think that it definitely can't hurt, it can only help. So I'm a fan of it. Knowing that there's restrictions. I told patients that there's a lot of unknown. But we know that's not gonna hurt you and it could possibly help you. So why not okay. And it's totally acceptable to check for vitamin D, not just in those without sun exposure, but in those that are considered at risk, which a majority of us are not going outside and getting their vitamin D unless they're taking supplements. Okay? All right. Now it's not advised to be over supplemented. I'm not making that claim. I'm just saying with a rational, normal, common sense approach, which seems to be lacking currently. Let's do this with a common sense, rational way of doing things. Okay? So anyway, current Opinions in Obstetrics and Gynecology 2020, let me give you this publication. As we get close to our review of what we're really trying to do, this title of this review by Bettis Lopez et al. Is Vitamin D Supplementation during Pregnancy An Overview. Now notice, remember, so far what I'm trying to do here is build a timeline and make the argument that, hey, we don't know if, if really doing something here to supplement. We don't know if that's very helpful or not. Okay, so what they did is that they took a look at all of the recent evidence, they took a look at randomized clinical trials, meta analyses to look at vitamin D supplementation and look at some perinatal outcomes. So this wasn't their own study. They're like, let's see what's out there. Let's take a look at it to see if supplementation potentially, potentially could be helpful. Now again, their levels of supplementation did vary. I mean, some were 600 IUs per day, some used a thousand, some have used up to 4,000. So there's a lot of variance there. But very quickly, quote, recent evidence from vitamin D intervention studies and meta analyses of a large number of studies support vitamin D supplementation during pregnancy to improve maternal, fetal and immediate and later offspring health. End quote. Did you all get this? Now, if you're thinking, well, why did the last one that we just covered, the SMFM thing, the do's and don'ts didn't, didn't mention that because this came out two years later. I want to read this again, guys. This is the big clinical pearl here and this is exactly what I'm trying to, trying to make the point here. Recent evidence from vitamin D intervention studies and meta analyses of a large number of studies support vitamin D supplementation during pregnancy to improve maternal, fetal and immediate and later offspring help. So here's the question. Does supplementation seem to help According to this 2020 data? Yes, it does. And that includes things like better bone mineral content for the child enamel Health and prevention of enamel deficiencies and some controversial data. I just want to be very clear. Some controversial data says could even help red Attention deficit hyperactivity disorder. Why not? So again, if it could possibly help, why shouldn't we be doing this? Which to which I say we should. So very quickly, our last review also comes out of 2024. Before we get into this new publication. This is February of 2023. So almost exactly two years from where we're recording this right now. Okay, now the caveat for this is that this was an MFM poster presentation. Okay, so this was at the, at the pregnancy meeting. This was not a full peer reviewed publication. This was a poster. Actually it was on Friday, February 10, 2023 and the title was Vitamin D deficiency during pregnancy and Perinatal and Long Term Outcomes. Okay, so taking a look again, does vitamin D deficiency. Not looking at supplementation, but that is deficiency linked to some issues. So let me give you this because this is a perfect setup as we launch into our main article of review and then we're done. Okay, so two years ago to the almost to the date that we're recording this quote, this is the first study to analyze the effects of maternal vitamin D deficiency during pregnancy on long term developmental outcomes as well as perinatal prognosis. Vitamin D deficiency in early pregnancy. Let's stop there. Y' all get this how you start the race. If you are totally deconditioned and you show up to the marathon going, I'm here, bro, I am here. I haven't run since PE High School and that's been 30 years. But I'm here at the starting line. You gotta have some problems, okay? You're gonna get some cramps, he's gonna take you out and you're gonna look like a fool. So that's my point is if you enter the race, if you enter the race unconditioned, it's gonna get you, it's gonna bite you in the ass. Same kind of deal. Pregnancy is a marathon. It's a hyper metabolic state. It's a physiological quote unquote stress response, which is physiologically nor. Okay, it's physiologically normal. I don't pathologicize pregnancy, but we have to be tuned in for it. That's why preconception consults are important. Well, women consults are important in reproductive age. Women in addition to a lot of other things. Okay, so quote, Vitamin D deficiency in early pregnancy. Here it is, guys. May increase the risk of neonatal respiratory distress syndrome, sepsis and even developmental delay. End quote. Not my opinion. Okay, this was out of SMFM as a poster presentation. This was a prospective study that covered 2017 and 2021, analyzing just over 500 singleton pregnant women who are otherwise called low risk. Okay? So this looked at perinatal outcomes and there you go. So is vitamin D deficiency linked to some issues? Nobody questions that. Yes, it is linked to issues according to who you read. And when you read it it's like, well, I don't know if supplementation helps it to help. Right, so supplementation does seem to help. That was our last buildup as. Until we get to what we were meant to talk about. All of that, guys, was just the, the, the prelude. Is that right? Prelude. Yeah, prelude. Right, prelude. The prelude to what we're talking about, which is the American Journal of clinical nutrition from February 2025. Very quickly, because I've already laid it out, you already know the gist of this. What I'm getting at the title is quote, maternal vitamin D status, fetal growth patterns and adverse pregnancy outcomes in a multisite prospective cohort study. End quote. First listed author is Celeste Beck et al. Okay, now this does come from the US or authors from Utah. So Salt Lake, there was people from Pennsylvania on here. There's Wexler Medical Center, Indiana's represented Pennsylvania and even on the west coast from University of Californ, Irvine. Right, so there's, it's again, multi site. So very quickly I'm just going to let this out and then we're done. I think I've already made my case here. Quote, we conducted a secondary analysis using data and samples from a multi site prospective cohort study of nullie Paris pregnant females in the United States. End quote. So let's stop there. Nulla Paris is good because that way you don't get muddied by prior OB history. Okay? So they keep saying, quote, we measured serum 25oHD. See, told you. That's what you're supposed to measure for 351 participants at 6 through 13 and 16 through 21 weeks of gestation. They then tracked fetal growth. They looked at neonatal anthropometric measurements. And so really what they're looking at is a fetal growth issue. Okay? Now they defined vitamin D deficiency or insufficiency as less than 50 non moles per liter. Now remember what I said. Some use milligrams nanograms per milliliter, some use nanomoles per liter. This basically that 50 is the same as the 20 ngs per milliliter. Okay? Just in a different unit. So it's the same. They're using the same thing that we talked about. Very quickly, here it is, guys. Quote, first trimester 25 oh D is positively associated with linear growth. Low first trimester 25 oh. D is associated. Here it is. Here it is, guys. Brace yourselves with a higher risk of preterm birth. Second trimester 25D is not associated with fetal growth or with pregnancy outcomes assessed. End quote. In other words, here's the take home and we're done. How you enter this race, how you're conditioned and how your body is ready determines how this is going to go. So it seems to be how you enter pregnancy with vitamin D levels is going to be your biggest risk here, not only for neonatal growth trajectory, but also for preterm birth. And we're done now. Come on, guys, you gotta say that that was pretty sweet, right? I mean, so I tried to do. We went. Laid this, this whole thing out 2011, even though it was reaffirmed in 2024. It shouldn't have because we had data since that. I like that 2020 meta analysis that said, yes, it seems to help here. And my point is, can you get hypervitamin ptosis from vitamin D? I guess you can, but a lot of that you pee out. So as long as you take the recommended amount of at least 600ius per day with supplementation up to a thousand to 2000 something up to 4000 would be okay. That's a huge safety window. Why not? But please, what I would recommend is put signs up there for women who are going to the well. Women care and their reproductive age. Vitamin D is important, guys. It's good for immune health, it's good for overall functioning. There's very controversial, but some associations to mood imbalances slash disorders. Get that vitamin D checked or go sit yourself outside. All right, Podcast family, as always, we're thankful for you. We're glad you're part of our podcast family. Thank you for still your support for our show. We'll get into that a little later, but in any way, we thank you. We appreciate you. And now that we've said all that, now let's take it home. Podcast family, we really are thankful for you. We hope you enjoyed this episode. We'll see you next time on Clinical Pearls. Sam.