NSAID Use During Pregnancy Linked to Pulmonary Hypertension In Newborns

Alex Otto

Pharmacy Today. 2001;7(5) 

Introduction

NSAID use during pregnancy increases the risk of pulmonary hypertension in newborns, according to a recently published study. Yet, women commonly use the drugs while they are pregnant despite labels that warn against doing so.

In a case-control study published in the March issue of Pediatrics, meconium was collected from 101newborn infants and analyzed for the presence of ibuprofen (e.g., Advil -- Whitehall Robbins), naproxen (e.g., Aleve -- Bayer), indomethacin (e.g., Indocin -- Merck), and aspirin. Results from 40 infants with persistent pulmonary hypertension of the newborn (PPHN), an often fatal complication, were compared with those of 61 randomly selected, healthy, full-term infants.

Putting the Fetus at Risk

Overall, 49.5% of the meconium samples were positive for NSAIDs: 22.8% were positive for ibuprofen, 18.8% for naproxen,7.9% for indomethacin, and 43.6% for aspirin. PPHN was significantly associated with both the presence of at least one NSAID in the meconium and, in particular, the presence of aspirin,ibuprofen, or naproxen.

NSAIDs block the synthesis of prostaglandins and thromboxane, which are needed to keep open the ductus arterious, the blood vessel that shunts blood past the lungs in the fetus. When the vessel closes early, pulmonary hypertension results. Since NSAIDs cross the placenta easily and have a prolonged half-life in the fetus, they should be avoided during pregnancy, especially in the last trimester

Although other studies have suggested a link between NSAIDs and PPHN, this is the first time an association has been clearly demonstrated, according to co-author Enrique M. Ostrea Jr, MD, professor of pediatrics at Wayne State University and chief of pediatrics at Detroit's Hutzel Hospital.

In the February 3 edition of BMJ, European researchers reported a tentative connection between NSAID use and an increased risk of miscarriage. The odds ratios of women receiving an NSAID prescription in the last week before a miscarriage was 6.99; the odds ratio dropped to 2.69 when an NSAID prescription had been taken 7 to 9 weeks before miscarriage.

Labeling Ignored by Patients

The authors of the Pediatrics study were surprised by the widespread use of the drugs. Use was grossly underreported as well, a finding confirmed by other researchers.

Women are thought to forget taking such common, everyday products and may not recognize their presence in multi-ingredient OTC medications. The widespread, easy availability of NSAIDs may also lull pregnant women into a false sense of safety.

The Pediatrics authors called for a reevaluation of the easy access pregnant women have to OTC NSAIDs as well as effective promotion of the dangers the drugs pose to the fetus.

Ostrea thinks the solution lies in stricter labeling, similar to what already exists on tobacco and alcohol products. Labeling should state explicitly that use could cause potentially fatal lung damage in infants, Ostrea said. "Similar statements on alcohol and cigarette labels have significantly reduced use during pregnancy."

He does not think it is necessary to place NSAIDs in a third, pharmacist-only drug class because all patients, not just pregnant women, use the products. Pharmacists should, however, warn pregnant women of the risks involved if they see them buying NSAIDs.

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