What is the safety of ibuprofen (nonsteroidal anti-inflammatory drug, NSAID) during the first trimester of pregnancy?

From the Guidelines

Ibuprofen should be avoided during the first trimester of pregnancy unless absolutely necessary and under the guidance of a healthcare provider. The safety of ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), during the first trimester of pregnancy is a concern due to its potential effects on the developing fetus and the pregnancy itself 1. While NSAIDs are not known to be teratogenic in humans, animal models suggest that they can block blastocyst implantation, which is a consideration for women trying to conceive 1.

Key Considerations

• The use of NSAIDs like ibuprofen close to term can lead to several potential maternal and fetal effects, including prolonged gestation and labor, increased peripartum blood loss, and increased anemia in the mother, as well as increased cutaneous and intracranial bleeding, premature closure of ductus arteriosus, pulmonary hypertension, impaired renal function, reduced urine output, and reduced amniotic fluid volume in the fetus 1.
• The American Academy of Pediatrics considers ibuprofen safe for use during breastfeeding, but it is crucial to avoid NSAIDs when breastfeeding a neonate with jaundice due to the potential risk of displacing bilirubin 1.
• Low-dose aspirin is generally considered safe throughout pregnancy but should be used with caution due to the potential risk of salicylate intoxication and bleeding problems in the neonate 1.

Recommendations

• If ibuprofen must be taken during the first trimester, it should be used at the lowest effective dose for the shortest duration possible.
• Acetaminophen (Tylenol) is typically considered a safer pain reliever option during pregnancy.
• It is essential to consult with an obstetrician or healthcare provider before taking any medication during pregnancy to weigh the potential benefits against the risks for the specific situation.

From the FDA Drug Label

Use of NSAIDs, including ibuprofen tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. There are no adequate, well-controlled studies in pregnant women. Ibuprofen tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus

The safety of ibuprofen during the first trimester of pregnancy is not well established.

• Key risks associated with NSAID use during pregnancy include premature closure of the fetal ductus arteriosus and fetal renal dysfunction.
• Animal studies have shown increased pre- and post-implantation loss and impaired kidney development with prostaglandin synthesis inhibitors like ibuprofen.
• Human data are limited, and there are no adequate, well-controlled studies in pregnant women.
• Ibuprofen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus 2.

From the Research

Safety of Ibuprofen During the First Trimester of Pregnancy

• The use of ibuprofen during the first trimester of pregnancy has been studied in several research papers 3, 4, 5, 6.
• A study published in 2021 found that exposure to ibuprofen in the first trimester can interfere with early nephrogenesis and cause abnormalities in developing kidney structures 3.
• However, another study published in 2018 found no significantly increased risk of major birth defects or spontaneous abortions after exposure to ibuprofen in the first trimester 4.
• A review article published in 2016 recommended that ibuprofen be used with caution during pregnancy, and only when the benefits outweigh the risks, as it can cause premature closure of the ductus arteriosus and impairment of fetal kidney function after 28 weeks of gestation 5.
• A study published in 2012 found that NSAIDs, including ibuprofen, can cause embryo-fetal and neonatal adverse effects, depending on the type of agent, dose, and duration of therapy, as well as the period of gestation 6.
• While a study on naproxen exposure during the first trimester found no significant teratogenic effect, it recommended that better-studied NSAIDs like ibuprofen be preferred in the first and second trimester of pregnancy 7.