The Media Line: Large-Scale Israeli Study Finds No Increased Birth Defect Risk From Common Pregnancy Painkillers

Large-Scale Israeli Study Finds No Increased Birth Defect Risk From Common Pregnancy Painkillers  

By The Media Line Staff  

Researchers at Ben-Gurion University of the Negev have published two large-scale studies involving more than 264,000 pregnancies that found no evidence linking commonly used pain medications during pregnancy to an increased risk of birth defects.  

The studies, published in PLOS Medicine and Human Reproduction Open, were led by Dr. Sharon Daniel and drew on two decades of clinical information collected through the siPREG (Southern Israeli Pregnancy Registry), which tracks maternal and fetal health outcomes.  

One study examined the use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), including ibuprofen products such as Advil and Nurofen, during the first trimester of pregnancy. Researchers reviewed 264,858 pregnancies documented at Soroka University Medical Center between 1998 and 2018, including more than 20,000 pregnancies involving NSAID exposure.  

Although birth defects initially appeared slightly more common among women who used NSAIDs, researchers reported that the difference disappeared after adjusting for factors including fever, pain, inflammatory diseases, chronic illnesses, and maternal background characteristics.  

“The results showed that NSAID medications are safe to use during the first trimester and are not associated with the development of congenital malformations,” Dr. Daniel stated.  

The second study focused on acetaminophen, also known as paracetamol and sold under brand names including Acamol and Tylenol. Researchers investigated potential links between exposure during pregnancy and outcomes including congenital malformations, stillbirth, low birth weight, low Apgar scores, newborn kidney failure, and premature closure of the ductus arteriosus.  

Paracetamol exposure was reported in 15.5% of pregnancies during the first trimester and 14.1% during the third trimester. Researchers found no independent association between the medication and adverse pregnancy outcomes after adjusting for medical and pregnancy-related factors.  

“At first glance, raw data might suggest a slight increase in birth defects among women who took these medications,” said Dr. Daniel. “However, our analysis revealed that the risk was actually tied to the mother’s underlying condition—such as a high fever, infection, or chronic illness—rather than the painkillers themselves.”  

To address concerns about unreported over-the-counter medication use, the research team conducted additional analyses.  

“We had to ensure that ‘real-world’ habits didn’t skew our results,” said co-author Dr. Ariel Hassidim. “We demonstrated that the volume of unreported use would have to be impossibly high.”  

The multidisciplinary team included researchers from Ben-Gurion University, Soroka University Medical Center, Schneider Children’s Medical Center, and Ariel University.