BEERSHEBA — Ben-Gurion University of the Negev published a study indicating no link between first-trimester NSAID use and major congenital malformations. The study also found no independent association between paracetamol use throughout pregnancy and adverse perinatal outcomes.

Researchers at Ben-Gurion University of the Negev conducted the study, which analyzed over 264,000 pregnancies documented at Soroka University Medical Center between 1998 and 2018. The analysis included pregnancies that concluded in either birth or termination due to suspected fetal abnormalities.

The study found no link between first-trimester NSAID use and malformations in the heart, central nervous system, musculoskeletal system, digestive system, or urinary system. Similarly, no association was found between paracetamol use and birth defects, stillbirth, or low birth weight. The investigation also determined that third-trimester use of paracetamol did not show an increased risk of newborn renal failure or heart-related complications.

Over 20,000 women in the study cohort reported taking NSAIDs during pregnancy. The raw rate of birth defects was 8.2% in pregnancies exposed to NSAIDs compared to 7.0% in unexposed pregnancies. For acetaminophen, the raw rate of birth defects was 7.9% in exposed pregnancies compared to 6.9% in unexposed pregnancies. However, after adjusting for factors such as fever, inflammatory diseases, pain, maternal background characteristics, and chronic illnesses, experts found this association between painkiller use and birth defects disappeared.

Senior pediatrician Sharon Daniel noted, "Our results suggest that paracetamol use throughout pregnancy is not independently associated with adverse perinatal outcomes, and that commonly used NSAIDs in early pregnancy are not associated with an increased risk of major congenital malformations." Daniel added, "However, our analysis revealed that the risk was actually tied to the mother's underlying condition – such as a high fever that can itself pose risks because prolonged high body temperature and inflammation, possibly affecting fetal development and pregnancy outcomes, infection, or chronic illness – rather than the painkillers themselves." She clarified that NSAIDs are generally contraindicated in the third trimester due to concerns about premature closure of the ductus arteriosus and effects on fetal renal function. Daniel further commented, "When these medications are used appropriately for clear clinical indications, there is no reason for added anxiety based on the outcomes we studied."

Why It Matters

This study provides information regarding the use of common painkillers during pregnancy, specifically NSAIDs and paracetamol. The findings suggest that when factors like maternal health conditions are considered, the use of these medications may not independently increase the risk of major congenital malformations or adverse perinatal outcomes for the studied conditions. The data for the study was sourced from the siPREG (Southern Israeli Pregnancy Registry) and the results were published in PLOS Medicine and Human Reproduction Open.

The research did not address long-term neurodevelopmental outcomes. Daniel stated that this remains "The question of long-term neurodevelopmental outcomes was not addressed in their research and remains an important area of inquiry that should be examined in studies specifically designed to evaluate them."