New research from Israel provides reassurance to pregnant women and healthcare providers about the safety of common painkillers during pregnancy. A large-scale study conducted at Ben-Gurion University of the Negev (BGU) and published in international journals confirms that non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) do not increase the risk of birth defects when used during pregnancy.
According to the study, which analyzed over 264,000 pregnancies, NSAIDs such as ibuprofen (Advil/Nurofen) are safe during the first trimester. Paracetamol, widely used throughout pregnancy, was found to be safe even in the last trimester. The findings were published in the journals PLOS Medicine and Human Reproduction Open.
Dr. Sharon Daniel, a senior pediatrician and epidemiologist at BGU, explained that while initial data suggested a possible link between medication use and birth defects, the actual risk was tied to underlying maternal conditions like fever, infections, or chronic illnesses rather than the medications themselves.
A key contribution to the study came from the siPREG (Southern Israeli Pregnancy Registry), a detailed and reliable database that tracks maternal and fetal health outcomes over 20 years. The registry enabled researchers to analyze data from all pregnancies documented at Soroka University Medical Center between 1998 and 2018, including over 20,000 women who used NSAIDs during pregnancy.
“Our results show that paracetamol use during pregnancy is not independently associated with adverse perinatal outcomes,” said Dr. Daniel. “Similarly, NSAIDs used in the first trimester are not linked to an increased risk of major congenital malformations.”
The study also found that there was no increased risk of birth defects in major organ systems, such as the heart, central nervous system, or urinary system. However, the researchers emphasized that the raw data initially showed a slightly higher rate of birth defects among exposed pregnancies (8.2% vs 7.0%), but after adjusting for factors like fever and chronic conditions, the association disappeared.
Dr. Daniel noted, “The risk was primarily explained by pre-existing conditions requiring treatment, not the medications themselves. This supports treating the underlying illness rather than avoiding necessary medications due to unfounded safety concerns.”
The research also addressed recent concerns about paracetamol, which has been linked in some studies to neurodevelopmental issues like ADHD and autism. However, the BGU study found no independent association between paracetamol use and these outcomes.
“While previous studies have raised concerns, our data does not support a causal link between paracetamol exposure and adverse pregnancy outcomes,” Daniel added. “Pregnant women should not feel guilt for using medically necessary treatments and should rely on clinical judgment and evidence-based guidelines.”
“We expect the findings to influence international pregnancy guidelines once replicated in diverse populations,” he said. “Further research using the siPREG registry will continue to examine other medications used during pregnancy.”
The team developed a sensitivity analysis to account for unreported over-the-counter drug use, confirming that even with potential underreporting, the findings remained consistent.
“Our work underscores the importance of treating maternal fever and pain effectively during pregnancy, as these conditions themselves can lead to complications,” said Dr. Daniel. “Clinicians should prioritize evidence-based decisions and avoid unnecessary fears about the safety of common painkillers.”
While NSAIDs are contraindicated in the third trimester due to concerns about fetal renal function and premature closure of the ductus arteriosus, the study confirms their safety in the first trimester. For paracetamol, the researchers emphasized that current recommendations remain unchanged based on their findings.
The study involved a large cohort of Jewish and Bedouin populations in southern Israel, showing no significant differences in outcomes between these groups. This reinforces the broader applicability of the findings across diverse populations.
“We hope these findings will help shift the discussion toward more evidence-based reassurance for pregnant women and their healthcare providers,” Dr. Daniel concluded. “Medically indicated treatment should not be avoided based on outdated myths. Our data provides clarity and supports informed decision-making during pregnancy.”
