Having a little one growing in your belly brings a lot of joy but also major anatomical and hormonal changes. In some women, these changes are accompanied by symptoms such as morning sickness, heartburn, or acid reflux.
Things like constipation could also appear or worsen during pregnancy.
When these symptoms take a toll on you, you may want to use medications to feel better. A recent study in the US found that 69% of pregnant women take at least one medication. Among the most frequently taken ones were those for pain relief, gastrointestinal complaints, and sinus congestion or allergy [1].
But you probably wonder, are these medications safe for my baby? Well, not all are safe during pregnancy or while breastfeeding.
Unfortunately, there’s a lack of high-quality studies in humans on the use of medications during this important time. Most associations with birth defects come from animal studies using very high doses, or from observational studies that many times fail to account for all confounding factors.
Until 2015, the FDA required all drug companies to categorize their medications into a letter that summarized their safety during pregnancy. You may still find references to this letter system on the Internet:
- A: Controlled studies in pregnant women fail to demonstrate a risk to the baby in the first trimester, there is no evidence of risk in later trimesters, and the possibility of harm appears remote.
- B: Animal-reproduction studies have not demonstrated a risk to the baby, but there are no controlled studies in pregnant women. Or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).
- C: Either studies in animals have revealed adverse effects on the baby and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
- D: There is positive evidence of risk to a baby during pregnancy, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
- X: Studies in animals or humans have demonstrated fetal abnormalities or there is evidence of risk based on human experience, or both. In this case, the risk of the drug clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
Not very clear, right? That’s why in 2015, the FDA requested drug companies to remove these letters and replace them with more detailed information about the safety and risks of each medication.
Now let’s take a look at the most common medications women take during pregnancy or while breastfeeding, whether these are safe or not for the baby, and how their use may impact a mom’s gut microbiome and her baby’s long term health.
Medications for pain relief
Non-steroidal anti-inflammatory drugs (NSAIDs)
NSAIDs are used to relieve inflammation, pain, and fever. Examples are:
- Ibuprofen (Advil®, Genpril®, Motrin®)
- Naproxen (Aleve®)
- Aspirin
These are all classified as C/D drugs.
In 2020, the FDA announced that pregnant women shouldn’t use NSAIDs at 20 weeks or later unless specifically advised to do so by their provider, because these medications may cause kidney problems in the unborn baby [2].
But in some specific cases, NSAIDs may still be prescribed during pregnancy. If so, use between weeks 20 to 30 is suggested to be limited to the lowest effective dose and shortest duration possible.
A special case is aspirin. Even if there’s evidence of human fetal risk [3], its use may be acceptable if, for example, other safer drugs cannot be used or are ineffective [4].
Low-dose 81 mg aspirin can be used at any point in pregnancy under the direction of a healthcare professional.
During breastfeeding, ibuprofen is considered safe for the baby because it reaches breastmilk at very low levels, and no adverse effects have been reported [5]. Instead, naproxen levels in breastmilk are low but there are a few reports about adverse effects [6]. High doses of aspirin for several days may also lead to some adverse effects on the baby [7].
Acetaminophen
Acetaminophen (known as paracetamol in Europe, sold as Tylenol®, Apra®, and Mapap®) also relieves fever and pain. But unlike NSAIDs, it doesn’t reduce inflammation. It’s by far the most used medication during pregnancy, with about 65% pregnant women using it in the US [8].
Acetaminophen is classified as a B drug for pregnancy. Given the adverse effects of NSAIDs on the baby, it is the preferred choice for the treatment of high fever and severe pain.
But it should still be used with caution.
Some studies have reported associations between acetaminophen use during pregnancy and male reproductive tract abnormalities like undescended testicles [9]–[11] and a shorter distance between the anus and the genitals [12], [13]. These abnormalities may affect the correct functioning of testicles during adulthood [14]. Most of these associations are seen when acetaminophen is used every day for more than 2 weeks.
During breastfeeding, acetaminophen seems to be generally safe. It reaches breastmilk in low levels and adverse effects on the baby are rare [15].
It’s worth mentioning that acetaminophen is a component of many over-the-counter medications used to relieve the symptoms of the flu or the common cold. Examples are Dayquil®, NyQuil®, ComTrex®, and Advil dual action®. So caution should be used not to mix these medications [16]. This is because acetaminophen overdose can lead to severe liver toxicity and renal failure.
NSAIDs, acetaminophen, and the gut microbiome
Do these medications have any effect on the gut microbiome? They do.
A study looked at people who took NSAIDs and compared their gut composition to people who didn’t [17]. As it turns out, different types of NSAIDs impact different types of gut bacteria.
For example, naproxen generated an increase in unfriendly bacteria from the family Enterobacteriaceae. Members of this family are related to gut inflammation.
On the other hand, ibuprofen was associated with higher levels of Prevotella and Alistipes, species that are generally considered friendly.
There are no such studies for acetaminophen, only laboratory studies that suggest it shouldn't affect the growth of common gut microbiome members [18]. This needs to be confirmed in humans.
Associations between prenatal acetaminophen exposure and neurodevelopmental disorders in the child.
In 2016 and 2017, the FDA and the Society for Maternal and Fetal Medicine Publications committee released announcements stating that the weight of evidence was inconclusive regarding a possible connection between acetaminophen use in pregnancy and Attention-Deficit/Hyperactivity Disorder (ADHD) in children [19], [20]. The European Medicines Agency also stated that the evidence was inconclusive.
They suggested that pregnant women should use acetaminophen only when necessary and at the lowest dose possible.
While these agencies consider the evidence to be inconclusive, there are several studies reporting a link between prenatal acetaminophen exposure and a higher risk of developing health issues later in life. Therefore, scientists caution against the use of acetaminophen during pregnancy and stress the importance of conducting well-designed studies [21].
Many observational studies have found a positive association between prenatal exposure to acetaminophen and ADHD [22]–[27], autism spectrum disorder (ASD) [26], [28]–[30] and other neurodevelopmental issues [30]–[32].
But one of the disadvantages of observational studies is that they usually rely on the mom recalling what medications she took during pregnancy, in which trimester, and in what dose.
Not providing the correct information may lead to incorrect associations.
To overcome this limitation, one study looked for acetaminophen in the umbilical cord [29] and another one in meconium [27].
Both found a positive association between prenatal exposure to acetaminophen and ADHD.
Associations between prenatal acetaminophen exposure and asthma
Five systematic reviews that re-analyzed different observational studies concluded that the risk of asthma or wheezing was higher in children exposed to prenatal acetaminophen [33]–[37].
However, some scientists believe that these associations should be interpreted with caution, as some studies didn’t consider all confounding factors in their analysis [21], [38]. For example, it’s important to know whether the mom or the dad has asthma or another respiratory condition, as these can be inherited and may be the true cause of increased risk of asthma in children.
Another study found that acetaminophen was associated with increased risk of asthma in a dose-dependent way [39]. However, when looking at the siblings of children, this association was not reproduced, pointing out that the association was not causal.
Associations between prenatal acetaminophen exposure and atopic dermatitis
Results are contradictory for atopic dermatitis, as one study found a positive association between prenatal acetaminophen exposure and increased risk of this condition [40], whereas another one found that prenatal exposure decreased the risk [41].
So, is acetaminophen safe to take during pregnancy?
Whether to take or not a medication during pregnancy involves a benefit-risk assessment. For example, high fever is known to be dangerous for both mom and baby [42], so in that case, taking acetaminophen may provide more benefits than risks.
Ideally for acetaminophen, you may want to consider taking it only when strictly necessary, with the lowest effective dose, for the shortest time possible. A good idea is to always ask your provider for guidance on this.
Medications for nausea and vomiting
Nausea and vomiting are very common during pregnancy. This is often referred to as “morning sickness,” which is a bit misleading. Signs of nausea and vomiting can occur at any time during the day.
Suggested first line treatment for mild nausea and vomiting is diet and lifestyle modifications [43]. These include:
- Eat as soon as you feel hungry. Having an empty stomach may aggravate nausea.
- Eat slowly and frequently throughout the day.
- Drink liquids 30 minutes before or after having solids.
- Try to avoid triggers like coffee and spicy foods.
- Cold foods may be better tolerated than hot foods, as they will have less smell.
For moderate symptoms that won't go away with these changes, ginger tablets may help. Acupuncture and acupressure may also help but results vary among studies [43].
If any of these lifestyle changes don’t work for you, it’s okay to use medication. Common medications used to treat nausea and vomiting during pregnancy are:
- Pyridoxine (vitamin B6)
- The antihistamine doxylamine (Unisom®)
- A combination of doxylamine and pyridoxine (Diclegis®, Bonjesta®, Diclectin®)
Doxylamine/pyridoxine is one of the few medications categorized as an A drug for pregnancy. Studies have shown it’s safe for the baby [44]. During breastfeeding, occasional use of doxylamine is thought to be safe for the baby. Prolonged use may cause temporary drowsiness, irritability, or colic [45].
Bismuth subsalicylate (Pepto-Bismol®) is a common medication used for the treatment of nausea and vomiting. It shouldn't be used during pregnancy or while breastfeeding without checking with your provider first.
There are no human studies evaluating if doxylamine and/or pyridoxine have an impact on the gut microbiome. Laboratory experiments suggest that doxylamine shouldn’t affect the growth of common gut microbiome members [18], but this needs to be confirmed in humans.
Medications for the common cold
The common cold is caused by viruses and it usually goes away on its own without treatment. Medications are commonly used to relieve symptoms such as cough, nasal congestion, and sore throat.
Common medications for cold relief include:
- Dextromethorphan+guaifenesin (Robitussin®)
- Nasal decongestants like pseudoephedrine and phenylephrine
- Any Tylenol®-based combination (you can read about Tylenol® or acetaminophen in the section about pain relief)
- Antihistamines (we’ll discuss these in the sinus/allergy section)
Dextromethorphan is a cough suppressant. One clinical trial found that its use during pregnancy didn’t increase the risk of birth defects [46]. An observational study found the same [47]. But it’s still classified as a C drug for pregnancy. Its levels in breastmilk are very low, so they aren’t expected to have any effects on the baby [48].
Guaifenesin is an expectorant that helps loosen congestion in the chest and throat. Its safety during pregnancy isn’t clear, so it’s classified as a C drug for pregnancy, and it’s recommended to avoid it during the first trimester [49]. It’s not known whether it would affect the baby during breastfeeding because its levels on breastmilk haven’t been measured. But scientists believe it’s unlikely to have adverse effects [50].
Pseudoephedrine and phenylephrine are decongestants commonly found in over-the-counter medications for colds. They are categorized as C drugs for pregnancy. Associations between their prenatal use and birth defects are not clear, as results vary among studies, and there are several limitations to drive strong conclusions [51]–[54]. It’s recommended to avoid their use during the first trimester.
Pseudoephedrine and phenylephrine are not expected to cause any adverse effects in breastfed babies, but pseudoephedrine has been reported to cause irritability and agitation. Something very important to mention is that these medications can reduce the amount of breastmilk produced, so they aren’t recommended for moms with low milk production [55], [56].
There are no human studies evaluating if these medications have an impact on the gut microbiome. Laboratory experiments suggest that diphenhydramine, dextromethorphan, guaifenesin, and acetaminophen shouldn’t affect the growth of common gut microbiome members [18].
An alternative to relieve cough and sore throat are cough drops made with menthol.
Menthol acts as a local anesthetic and gives a cooling sensation. Look at the ingredients though, because cough drops may contain other ingredients like dextromethorphan.
Medications for sinus/allergic rhinitis
When we have an allergic reaction, our body releases a substance called histamine. Histamine is recognized by histamine receptors in our cells, leading to all kinds of allergy symptoms.
Allergy symptoms are treated with medications called antihistamines. These prevent cell receptors from recognizing histamine. So histamine will still be produced, but our body won’t react to it.
About 7-15% pregnant women take antihistamines [8]. Some examples of antihistamines are:
- Fexofenadine (Allegra®)
- Diphenhydramine (Benadryl®)
- Loratadine (Claritin®)
- Cetirizine (Zyrtec®)
- Chlorphenamine (ChlorTabs®)
- Desloratadine
Antihistamines are categorized as B or C drugs for pregnancy. Different observational studies have looked at their prenatal use and their association with birth defects, but findings have been inconsistent [57]–[60]. So it can’t be strongly concluded that exposure to antihistamines during early pregnancy is associated with birth defects.
For example, a study with about 41,000 pregnancies looked for associations between prenatal antihistamine use and birth defects. It found positive associations for cetirizine, loratadine, fexofenadine, and others [59]. But another study with about 1,287,000 pregnancies, compared fexofenadine against cetirizine, and didn’t find any associations with birth defects [60].
A 2014 systematic review that looked at 54 studies reported that only 9 of these found positive associations between prenatal antihistamine use and birth defects [58].
During breastfeeding, the safer alternatives seem to be:
- Loratadine and cetirizine, as both reach breastmilk at low levels and most studies have reported no adverse effects on the baby [61], [62].
- Chlorphenamine and desloratadine are thought to be safe too, although their levels in breastmilk haven’t been measured directly and there are only a few studies looking at effects on babies, none of them reporting adverse effects [63], [64].
- Occasional use of diphenhydramine should be okay, whereas large doses or prolonged use may cause irritability, drowsiness, or colic in the baby [65].
- Fexofenadine hasn’t been measured in breastmilk, but its levels are thought to be low. It may cause irritability in some babies [66].
When used in high doses, and specially if used along with pseudoephedrine or phenylephrine, antihistamines may reduce the amount of breastmilk produced, so they aren’t recommended for moms with low milk production.
There are no human studies evaluating if these medications have an impact on the gut microbiome. But laboratory experiments have shown that loratadine affects the growth of several beneficial species, for example Bacteroides ovatus, Bifidobacterium adolescentis, Bifidobacterium longum. Fexofenadine inhibits the growth of unfriendly Escherichia coli, and chlorphenamine inhibits the growth of beneficial Akkermansia muciniphila. No effects were observed for diphenhydramine and cetirizine [18].
Below are some alternative ways to relieve allergy symptoms:
- Use a nasal saline spray to relieve nasal congestion. The saline solution helps loosen mucus and debris inside the nose.
- Stay hydrated. Drinking more water will help thin your nasal mucus.
- Inhale steam. Hold your head over a bowl or sink filled with warm water and place a towel over your head to trap the steam. This will help you breathe easily.
- Consider an air purifier with an HEPA filter.
- Add some exercise to your week. One study found that walking or running three times a week improved symptoms of rhinitis [67]. Another one found that practicing one hour of hatha yoga, three times a week also helped [68].
- Vitamin C may also help relieve allergy symptoms. Although most positive results come from the use of intravenous vitamin C [69], [70], one study found that a vitamin C nasal spray helped reduce symptoms in 74% people [71]. Another study looked at vitamin C pills, but it couldn’t be concluded if these really helped because they were tested along with exercise [67].
- If you are allergic to dust mites, clean and vacuum regularly.
- If you are allergic to pollen, keep windows and doors closed during periods when the pollen count is high. This will lower exposure.
- Shower when arriving home, to remove any allergens that may have stayed in your hair and skin.
Medications for constipation
For most people, constipation is fewer than three bowel movements a week. This uncomfortable situation occurs twice more in women than in men [72]. And about 13-38% pregnant women suffer from constipation [73].
There are many factors that may promote the development of constipation or its worsening during pregnancy:
- Hormone changes
- Anatomical factors
- Changes in water absorption
- Reduced physical activity
- Dietary changes
- Pregnancy medications or supplements [73]
Is the gut microbiome different in women with constipation? Probably yes. One study found that women suffering from constipation have, for example, lower levels of butyrate-producers than women with regular bowel movements [74].
Ideally, the first line of treatment for constipation are lifestyle changes.
For example, adding more fiber to the diet (fruits, veggies, whole grains, and beans) may help. One study showed that pregnant women who consumed 10 grams of fiber daily for two weeks had more bowel movements and softer stools than women who didn’t increase their fiber intake [75].
Drinking more water and adding some physical activity to your day may also help.
Another thing that may relieve constipation is assuming a "squat" position while pooping, with knees bent and torso leaned slightly forward. Sitting down and resting your feet on a small stool so that your knees are above your hips should also work. This will help the muscles relax and everything will go out more easily.
If these lifestyle modifications don’t work for you, then you may want to try some over-the-counter medications. These come in many different forms so let’s see each in detail.
Bulk fibers
Bulk fibers relieve constipation by absorbing water and increasing the volume of your stool. There are different types:
- Natural, e.g. psyllium husk and wheat dextrin
- Synthetic, e.g. polycarbophil (Fibercon®)
- Semi-synthetic, e.g. methylcellulose
As none of these fibers are absorbed, they are unlikely to have any negative effects on the baby if used during pregnancy or while breastfeeding. They are classified as B drugs for pregnancy.
If choosing bulk fibers, work gradually to avoid bloating and cramps. Start with a few grams and gradually increase until you reach the recommended dose.
These fibers take several days to act. So, if you need immediate results, these may not be the best choice.
Stool softeners
These compounds reduce the surface tension of the stool, which allows more water to be absorbed. The result, softer stools.
One example of stool softener is docusate sodium (Colace®), which is classified as a C drug for pregnancy. Some very old studies with pregnant women found no association between docusate sodium and baby malformations [76], [77], so it’s considered low-risk. It should also be safe to use during breastfeeding.
Osmotic laxatives
These compounds retain water in the gut, which results in increased stool frequency. There are different kinds:
- Lactulose. It's considered to be safe during pregnancy because it’s barely absorbed from the gut [78]. It’s classified as a B drug for pregnancy, and should be safe for the baby during breastfeeding too. But lactulose may not be the best choice for pregnant women, because it may cause nausea, cramps, and flatulence. One study reported no fetal abnormalities during follow-up [79].
- Polyethylene glycol, or PEG (MiraLAX®). It's thought to be safe during pregnancy and while breastfeeding because it's barely absorbed from the gut. It’s classified as a C drug for pregnancy because there aren’t many studies. One study reported no fetal abnormalities during follow-up and found out that PEG was more effective than lactulose to treat constipation during pregnancy [79]. Another study found that PEG was effective for 73% of pregnant women [80].
- Osmotic salts. Examples of these are magnesium oxide, magnesium hydroxide (milk of magnesia) and magnesium citrate. These salts are considered a low risk treatment during pregnancy if used short term [81]. They are also compatible with breastfeeding [82]. Be careful with long term use because it may lead to sodium retention or too much magnesium in the blood.
Stimulant laxatives
Examples are senna (Senokot®) and bisacodyl. These compounds stimulate intestinal movement and alter electrolyte transport. The FDA classified them as category C, and they are considered a low risk treatment for constipation during pregnancy if used short term.
But use stimulant laxatives with caution and only after bulk and osmotic laxatives have failed.
No association has been found between senna and baby malformations [83], [84]. Senna is excreted in breastmilk as an active metabolite named rhein. One study showed no effects on babies while breastfeeding [85], but again should be used as a third option.
There are no studies evaluating the safety of bisacodyl during pregnancy, but it's considered low risk. It appears to not reach breastmilk so it can be used safely during breastfeeding [86].
Effect of medications for constipation relief on the gut microbiome
If these medications change the stool composition, one may expect they have an impact on the gut microbiome. Do they?
Some of them have been studied in this regard:
- One study found psyllium husk increased the levels of Ruminococcaceae and decreased the levels of Enterobacteriaceae [87]. Some of the beneficial bacteria that belong to the Ruminococcaceae family are Faecalibacterium prausnitzii and Ruminococcus bicirculans. On the other hand, the Enterobacteriaceae family is composed of unfriendly bacteria like Salmonella enterica and Escherichia flexneri. Another trial found that psyllium husk increased the levels of Faecalibacterium and Veillonella; and increased the production of short-chain fatty acids [88].
- Laboratory experiments found that wheat dextrin increased the levels of the Bacteroidaceae family [89]. Bacteroides species, which are generally friendly fiber degraders, belong to this family.
- Lactulose is fermented by gut bacteria, so at low doses it acts as a prebiotic and promotes the growth of beneficial Bifidobacterium [90]. It’s not clear whether these effects occur at high doses like the ones used to relieve constipation.
- PEG can’t be digested by gut bacteria so it shouldn’t have any effect on the gut microbiome.
- Animal experiments showed that senna modifies the gut microbiome by, for example, increasing the levels of beneficial Akkermansia [91].
Medications for bloating
Bloating occurs when your belly feels full and tight, often due to the accumulation of gas.
Simethicone (Gas X®, Mylanta®) is an anti-foaming medication that theoretically helps gas bubbles to pass more easily through the gut.
Simethicone is considered low-risk during pregnancy, although it’s classified as a C drug during pregnancy. It’s not absorbed so it shouldn’t have any negative effects on the baby. It should also be safe if used while breastfeeding.
There are no studies evaluating if simethicone has an impact on the gut microbiome.
Would you prefer some alternative ways to relieve bloating? Try some of these:
- Physical activity. Go for a walk! This will help your bowels move more, which can help release excess gas.
- Replace sodas with water. Carbonated drinks contain gas that may build up in the stomach. Sugar or artificial sweeteners in these beverages may also contribute to gas production. If you suffer from bloating, water is your best friend.
- Keep a food diary. You may be sensitive to certain foods like dairy, gluten, or raw vegetables. So tracking what you ate before your symptoms appear, can help you identify trigger foods.
Medications for heartburn and acid reflux
The lower esophageal sphincter (LES) is a ring of muscle that lies between the stomach and the esophagus. It acts as a valve that prevents the stomach acid from leaking up into the esophagus. When working correctly, the LES is always closed, except when we eat to allow the passage of food.
When the LES doesn’t close properly, the stomach acid spills up and irritates the esophagus, causing heartburn and/or acid reflux.
About 30-50% of pregnant women suffer from heartburn or acid reflux because changes in hormones cause the LES to relax. Another not minor factor that may contribute is having a baby in your belly, which compresses the stomach [92].
If you suffer from these conditions during pregnancy, the suggested first line treatments are lifestyle changes.
Changing certain habits may help to reduce mild symptoms. For example, you could:
- Try eating smaller amounts of food. Large meals may exacerbate the symptoms.
- Avoid dietary triggers when possible. This includes chocolate, mints, caffeine, and spicy or acidic foods.
- Try not to eat within three hours of bedtime. Eating too close to bedtime increases the risk of having reflux at night [93].
- Raise the head of your bed.
- Try acupuncture to manage heartburn and reflux [94].
If symptoms persist or are severe, medications may be used. Let’s see the different types of medications and whether these are safe to be used during pregnancy.
Antacids
Antacids don’t stop the stomach acid production, they just neutralize it. They provide fast relief and are suggested as the first option if lifestyle changes don’t work.
Ingredients in antacids include magnesium, aluminum, or calcium salts.
Some examples are Maalox® and TUMS®.
Antacids don’t have an FDA classification, but they are considered safe during pregnancy and breastfeeding. One clinical trial reported no adverse effects on babies from pregnant women who took Maalox® [95].
Alginates
Alginates also contain magnesium, aluminum, or calcium as ingredients. But they are different from antacids. One example is Gaviscon®.
Once in the stomach, alginates create a gel barrier that prevents the acid from spilling out of the stomach.
Alginates are considered safe to use during pregnancy and breastfeeding. Two clinical trials studied Gaviscon® use during pregnancy and found no association between the medication and adverse effects on the baby [95], [96].
Sucralfate
This medication is mostly used to treat stomach ulcers but also has antacid activity. It’s minimally absorbed from the gut so it’s considered safe during pregnancy, and it should also be safe during breastfeeding. Animal studies have shown it’s safe, and there are no reports of adverse effects for human babies.
But as there are not enough clinical trials, sucralfate is classified as category B for pregnancy.
Histamine-receptor agonists (HRAs)
These medications inhibit the production of stomach acid. Examples are famotidine (Pepcid®), cimetidine (Tagamet®), and ranitidine (Zantac®). Different clinical studies have shown that HRAs don’t cause baby malformations or pregnancy complications [97]–[100]. Still, they are classified as category B drugs, because animal studies showed some adverse effects for high doses of cimetidine [101], which haven’t been replicated in humans.
HRAs reach breastmilk at very low concentrations, so they aren’t expected to cause any adverse effects on the baby. Cimetidine may potentially interfere with the functioning of some hepatic enzymes, so other medications from this category should be preferred over this one during breastfeeding [102].
Proton pump inhibitors (PPIs)
Similar to HRAs, PPIs also inhibit the production of stomach acid, but through a different mechanism. Examples of PPIs are omeprazole and lansoprazole. All PPIs are classified as B drugs, except for omeprazole, which is category C.
In pregnant women, several studies found no adverse effects on babies, suggesting omeprazole should be safe [99], [103]–[106]. However, there are no large well-designed clinical trials on the safety of omeprazole during pregnancy, which is why it remains as a category C medication.
There’s also not much data on the safety of omeprazole during breastfeeding, but the drug levels in breastmilk during a standard treatment are very low, below those used for the treatment of newborns. One case study reported no adverse effects on the baby [107].
Lansoprazole and other PPIs are classified as B drugs even if there aren’t many large studies done with pregnant women. So far, studies indicate lansoprazole should be safe for the baby [104], [106]. There are no studies about the safety of other PPIs during breastfeeding, but like omeprazole, the concentration in breastmilk is lower than that used to treat newborns, so the assumption is that they are safe [108], [109].
Effect of acid-suppressive medications on the gut microbiome
Do any of these medications have an impact on the gut microbiome?
PPIs are by far the most studied. As it turns out, people who take PPIs have increased levels of bacteria belonging to the Streptococcaceae family [110]–[115], like Streptococcus anginosus [113] and Streptococcus vestibularis [110].
Streptococcus are bacteria commonly found in the mouth and throat, but they may also inhabit the gut. If the gut barrier is compromised and these bacteria are present in high numbers, they may cause trouble.
Scientists think that because PPIs inhibit the production of stomach acid, it’s easy for oral bacteria to pass through the stomach and colonize the gut.
Prenatal exposure to acid-suppressive medications and allergic disease
Some studies in animals and adults found that exposure to PPIs or HRAs resulted in allergic sensitization. This prompted scientists to look for an association between prenatal exposure to these medications and the development of allergy during childhood.
So far, a bunch of observational studies have looked at this possibility. These studies usually look at medical records from moms who were prescribed PPIs and/or HRAs during pregnancy and from moms who weren’t prescribed them. Then the studies evaluate whether the number of children that developed disease is greater for those moms who were prescribed the medications compared to those who weren't.
Some studies found that children from moms who took acid-suppressive medications were 1.23-1.57 times more likely to develop asthma than children whose moms didn’t take the medications [116]–[118].
One of these studies also found that children were 1.32 and 2.4 times more likely to develop atopic dermatitis and allergic rhinitis, respectively [118].
A meta-analysis of eight of these observational studies found out that children prenatally exposed to PPIs or HRAs had 1.34-1.57 higher risk of developing asthma. However, the authors of this analysis mentioned that the studies evaluated had several limitations and none of them took into account all the factors that may influence whether a child develops the diseases or not, besides the medications [119].
An interesting example is one big study that found a slight association between prenatal exposure to PPIs or HRAs and asthma, but it also found the same for moms who took the medications two years after giving birth, not during pregnancy [120].
How is this possible? Well, this highlights how difficult it is for observational studies to find true associations.
Asthma is an hereditary condition, and people with asthma often suffer from acid reflux. So it may be that moms who were prescribed acid-suppressive medications had asthma to begin with, or that the acid reflux itself interfered with the baby’s development in such a way that they were more likely to develop asthma in the future.
In conclusion, to clearly establish if acid-suppressive medications during pregnancy truly make the baby more prone to develop allergic disease, clinical trials should be done. Instead of looking at past events, a well-designed clinical trial will be able to compare in present time PPI and HRA use versus no use, and then follow the children for a number of years to see if they develop the disease.
In the meantime, if you have heartburn or acid reflux during pregnancy:
- Consider implementing some lifestyle changes first.
- If lifestyle changes don’t help improve your symptoms, then try antacids or alginates.
- Only then, if symptoms don’t subside, you may want to try PPIs or HRAs.
