Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn

Objective. The objective of this study was to detect fetal exposure to nons teroidal antiinflammatory drugs (NSAIDs) by meconium analysis and to determ ine the relationship between fetal exposure to NSAIDs and the development o f persistent pulmonary hypertension of the newborn (PPHN). Methods. In a case-control study of the inborn and outborn nurseries of a l arge urban medical center, meconium was collected from 101 newborn infants (40 with the diagnosis of PPHN based on clinical or echocardiographic crite ria and 61 randomly selected, healthy, term infants [control]) and analyzed for NSAIDs (ibuprofen, naproxen, indomethacin, and aspirin) by gas chromat ography/mass spectrometry. The risk of developing PPHN was determined in in fants who were exposed antenatally to NSAID. Results. Infants with PPHN (n = 40) had a mean gestation of 38.9 weeks and birth weight of 3524 g, which were similar to the those of the control grou p (n = 61). However, the incidence of low Apgar scores (less than or equal to6) at 1 minute and 5 minutes was significantly higher in the PPHN group t han in the control group. The diagnoses associated with PPHN were primary P PHN (25%), meconium aspiration syndrome (35%), respiratory distress syndrom e (20%), low Apgar score/asphyxia (12.5%), and pneumonia/sepsis (8%). Mean duration of ventilator support for the PPHN group was 11 days. Nitric oxide (NO) was given to 19 infants (47.5%) for a mean duration of 25.4 hours. Fo urteen of the 19 infants who were treated with NO (74%) required extracorpo real membrane oxygenation, and 2 died. The overall incidence of positive NS AID in meconium in the study population (n = 101) was 49.5%: 22.8% were pos itive for ibuprofen, 18.8% for naproxen, 7.9% for indomethacin, and 43.6% f or aspirin. There was poor agreement (Cohen's kappa = 0.09) between materna l history of NSAID use and NSAID detection in meconium. PPHN was significan tly associated with 1) the presence of at least 1 NSAID in meconium (odds r atio [OR] = 21.47; 95% confidence interval [CI] = 7.12-64.71) or 2) the pre sence in meconium of aspirin (OR = 8.09; 95% CI = 3.27-20.10), ibuprofen (O R = 12.89; 95% CI 3.93-42.32), or naproxen (OR = 3.31; 95% CI = 1.17-9.33). By logistic regression analysis, low Apgar scores at 1 and 5 minutes and t he antenatal exposure to aspirin, naproxen, and ibuprofen were significantl y associated with PPHN and treatment with inhaled NO or extracorporeal memb rane oxygenation. Conclusion. We confirm by meconium analysis the results of previous studies that demonstrated that the use of NSAIDs during pregnancy, particularly as pirin, ibuprofen, and naproxen, is high; is grossly underestimated by mater nal history; and is significantly associated with PPHN. Thus, the easy acce ss to over-the-counter NSAIDs of pregnant women should be reevaluated, and the potential dangers of these drugs to the newborn infant should be more e ffectively promoted.