Acetaminophen (Tylenol) is the safest over-the-counter pain reliever during pregnancy, and several other common medications are considered low-risk for specific symptoms. But the list of what’s off-limits is just as important as what’s safe, and timing matters: a medication that’s fine in the second trimester may pose real risks in the first or third.
Here’s what the current evidence says about medications for the most common pregnancy complaints, from headaches and allergies to heartburn and infections.
Pain Relief and Fever
Acetaminophen remains the go-to option. The FDA considers it the safest over-the-counter pain reliever and fever reducer available during pregnancy, ahead of every alternative. That said, the recommendation is to use the lowest effective dose for the shortest time possible. Some evidence suggests that taking acetaminophen continuously throughout pregnancy may carry more risk than occasional use, so it’s best reserved for when you genuinely need it rather than used routinely for low-grade fevers.
Ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin are a different story. These are all NSAIDs, and the FDA warns against using them at 20 weeks of pregnancy or later. After that point, NSAIDs can cause kidney problems in the developing baby, which may lead to dangerously low amniotic fluid levels. After 30 weeks, there’s an additional risk: premature closure of a blood vessel near the baby’s heart that needs to stay open until birth. One exception exists. Low-dose aspirin (81 mg) prescribed for specific conditions like preeclampsia prevention does not fall under this warning.
Morning Sickness
Vitamin B6 is the recommended first step for pregnancy nausea, either alone or combined with doxylamine (the antihistamine found in Unisom SleepTabs). This combination is the only FDA-approved treatment specifically for nausea and vomiting in pregnancy. The typical starting approach is two tablets at bedtime. If nausea persists into the next afternoon, the dose can gradually increase over several days to a maximum of four tablets daily, split between morning, mid-afternoon, and bedtime. Many women find bedtime dosing alone is enough to take the edge off morning nausea.
Allergies
Cetirizine (Zyrtec) and loratadine (Claritin) are the preferred second-generation antihistamines during pregnancy. Both have been widely studied and show no increased risk of birth defects. The American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology both recommend these options, particularly after the first trimester. Fexofenadine (Allegra) has less safety data and is generally considered a second choice.
Coughs and Colds
For coughs, dextromethorphan (the “DM” on cough syrup labels) has a solid safety record. Studies following hundreds of pregnancies exposed in the first trimester found no increased risk of birth defects. Guaifenesin, the expectorant that helps loosen mucus, has similarly reassuring data from multiple studies. Short-term use of both is considered safe.
Decongestants require more caution. Pseudoephedrine (Sudafed) should be avoided during the first three months, per ACOG guidelines. Some studies have found a small increased chance of specific birth defects with first-trimester use, including an opening in the baby’s abdominal wall. After the first trimester, occasional use is generally considered lower risk, but saline nasal sprays are a safer alternative throughout pregnancy.
Heartburn and Acid Reflux
Calcium carbonate antacids like Tums, Rolaids, Mylanta, and Maalox are safe for pregnancy heartburn. They also provide a small calcium boost. Avoid antacids containing sodium bicarbonate (baking soda), magnesium trisilicate, or aspirin, as these can cause problems during pregnancy. If over-the-counter antacids aren’t cutting it, your provider may suggest other options, but the basic calcium-based tablets handle most cases.
Infections and Antibiotics
Not all antibiotics are equal during pregnancy. The classes with the strongest safety profiles include penicillins (amoxicillin, ampicillin), cephalosporins, clindamycin, and metronidazole. These are the standard choices for common infections like urinary tract infections, strep throat, and bacterial vaginosis during pregnancy.
Several antibiotic classes are clearly harmful. Tetracyclines can damage developing bones and permanently discolor a baby’s teeth, and are not recommended after the fifth week of pregnancy. Fluoroquinolones should also be avoided. The aminoglycoside streptomycin has been linked to irreversible hearing loss in babies exposed during the first trimester. Sulfa antibiotics (like sulfamethoxazole/trimethoprim) carry risks of birth defects in the first trimester and other complications later in pregnancy.
Sleep Problems
Diphenhydramine (Benadryl, Unisom SleepGels) is commonly used as a sleep aid during pregnancy. Occasional use at recommended doses has not been shown to increase the risk of preterm birth or low birth weight. The data on birth defects is mixed: a few studies have suggested a slightly higher chance with first-trimester use, but others found no increase, and no consistent pattern has emerged.
In the third trimester, sticking to recommended doses is especially important. Reports of uterine contractions and rare fetal complications have been linked to doses higher than recommended or prolonged daily use. Babies exposed to diphenhydramine daily throughout pregnancy may also experience temporary withdrawal symptoms like tremors after birth.
Depression and Anxiety
SSRIs are the most studied class of psychiatric medication in pregnancy, and untreated depression carries its own serious risks for both mother and baby. Among SSRIs, sertraline (Zoloft) has the most favorable safety profile, with the lowest risk of a rare but serious newborn lung condition compared to other antidepressants. Some studies have linked SSRI use to slightly higher rates of preterm birth and a temporary adjustment period for newborns in the first few days after delivery. For many women, the benefits of staying on medication outweigh these risks, but this is a decision that involves weighing your specific situation.
Medications to Strictly Avoid
Some medications cause serious, well-documented harm to a developing baby. Isotretinoin (Accutane), used for severe acne, is one of the most potent known causes of birth defects. Methotrexate, used for autoimmune conditions and certain cancers, is similarly dangerous. Warfarin, a blood thinner, can cause skeletal abnormalities and nasal underdevelopment. High-dose vitamin A supplements (not the amounts found in prenatal vitamins) can cause heart and thymus defects.
The old FDA letter grading system for pregnancy safety (categories A, B, C, D, and X) was officially retired and replaced with a more detailed labeling format that includes a risk summary, clinical considerations, and available data for each drug. If you see those letter categories referenced, they’re outdated. Current drug labels are required to provide more nuanced, regularly updated information about use during pregnancy and breastfeeding.