Hidden Dangers of NSAID Use After 20 Weeks of Pregnancy

People widely use non-steroidal anti-inflammatory drugs (NSAIDs) for their analgesic, antipyretic, and anti-inflammatory properties. Commonly prescribed and over-the-counter NSAIDs, such as ibuprofen, naproxen, and diclofenac, offer significant benefits for pain management and inflammation control. However, their use during pregnancy, particularly beyond the 20th week, has raised considerable safety concerns. Pharmacovigilance specialists must be vigilant in understanding these risks to ensure maternal and fetal health.

The Role of NSAIDs in Pregnancy

NSAIDs function by inhibiting cyclooxygenase (COX) enzymes, which play a crucial role in synthesising prostaglandins. Prostaglandins are lipid compounds that perform various physiological functions, including modulating inflammation, pain, and fever and maintaining renal function and gastrointestinal integrity. During pregnancy, prostaglandins help regulate uterine contractions and keep the ductus arteriosus patency, a vital fetal blood vessel.

Risks of NSAIDs Use After 20 Weeks: A Critical Threshold

Research and clinical observations have identified several potential risks associated with prolonged NSAID use beyond the 20th week of pregnancy. These risks are particularly concerning due to the critical developments occurring during the second and third trimesters.

Fetal Renal Impairment and Oligohydramnios

NSAIDs can lead to fetal renal impairment, resulting in oligohydramnios—a condition characterised by low amniotic fluid levels. The inhibition of COX enzymes reduces fetal renal blood flow, decreasing urine output and, consequently, amniotic fluid production. Oligohydramnios can cause complications such as fetal growth restriction, preterm birth, and labor complications.

Constriction of the Ductus Arteriosus

Prolonged NSAID exposure can cause premature constriction or closure of the ductus arteriosus. This fetal blood vessel, which connects the pulmonary artery to the descending aorta, is crucial for diverting blood away from the non-functioning fetal lungs. Premature constriction can lead to right ventricular hypertrophy and heart failure in the fetus, posing severe health risks and necessitating immediate medical intervention.

Increased Risk of Miscarriage

Several studies suggest a correlation between NSAID use during pregnancy and an increased risk of miscarriage. The exact mechanism remains unclear, but it is hypothesised that prostaglandin inhibition may interfere with embryonic implantation and placental function.

Persistent Pulmonary Hypertension of the Newborn (PPHN)

NSAID-induced ductus arteriosus constriction is also linked to PPHN, a condition where a newborn’s circulatory system fails to adapt to breathing outside the womb. This can result in severe respiratory distress requiring intensive medical treatment.

Clinical Case Study Identified by DrugCard Platform

The DrugCard platform highlighted a clinical case from the medical literature, underscoring the risks associated with NSAID use during pregnancy.

A newborn was admitted to the NICU five hours post-delivery with severe respiratory failure and was oxygen-dependent. The baby was delivered via emergency cesarean section due to a prenatally diagnosed prematurely closed ductus arteriosus.

The mother had an acute respiratory viral infection a week before delivery and was treated with high doses of over-the-counter ibuprofen.

A 2D echocardiogram revealed severe right ventricular hypertrophy and tricuspid insufficiency due to the premature closure of the ductus arteriosus. The infant was placed on continuous positive airway pressure (CPAP) ventilation to reduce pulmonary vascular resistance and the right ventricle’s afterload. The infant’s condition improved significantly over the next 3-4 weeks. The right ventricular hypertrophy regressed to normal, and the child grew and developed appropriately for their age.

Regulatory Warnings and Recommendations for NSAIDs Use

Given these potential risks, regulatory agencies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have issued warnings against the prolonged use of NSAIDs after the 20th week of pregnancy. They recommend:

Avoiding NSAIDs During Pregnancy. Whenever possible, alternative pain management strategies should be employed significantly beyond the 20th week.

Consultation with Healthcare Providers. Pregnant women should consult healthcare providers before using NSAIDs. If NSAIDs are deemed necessary, they should be used at the lowest effective dose and for the shortest possible duration.

Monitoring for Adverse Effects. Pregnant women using NSAIDs should be closely monitored for signs of oligohydramnios and other complications. Ultrasound examinations can help assess amniotic fluid levels and fetal well-being.

The Role of Pharmacovigilance Specialists

Pharmacovigilance specialists play a pivotal role in monitoring, evaluating, and mitigating the risks associated with NSAID use during pregnancy. Key responsibilities include:

Data Collection and Analysis. Gathering and analysing data on adverse drug reactions (ADRs) from various sources, including clinical trials, case reports, and post-marketing surveillance.

Risk Communication. Disseminating information about the potential risks of NSAIDs to healthcare providers and patients. This includes updating labelling, providing educational materials, and issuing safety alerts.

Policy Development. Collaborating with regulatory authorities to develop guidelines and policies that promote safe medication practices during pregnancy.

Conclusion

While NSAIDs are effective for managing pain and inflammation, their use during pregnancy, particularly after 20 weeks, poses significant risks to fetal health. Pharmacovigilance specialists must stay informed about these risks, promote safe medication practices, and ensure that pregnant women and healthcare providers know the potential dangers. Additionally, it is crucial to highlight the importance of continuously monitoring medical literature. Identifying cases like the one described enables professionals to develop new strategies to minimise risks, such as informing consumers and updating safety guidelines. Therefore, vigilant monitoring and proactive communication can safeguard the safety of mothers and their unborn children.