Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. Pediatrics 2001 Mar;107(3):519-23
Date
03/07/2001Pubmed ID
11230592DOI
10.1542/peds.107.3.519Scopus ID
2-s2.0-0035120389 (requires institutional sign-in at Scopus site) 179 CitationsAbstract
OBJECTIVE: The objective of this study was to detect fetal exposure to nonsteroidal antiinflammatory drugs (NSAIDs) by meconium analysis and to determine the relationship between fetal exposure to NSAIDs and the development of persistent pulmonary hypertension of the newborn (PPHN).
METHODS: In a case-control study of the inborn and outborn nurseries of a large urban medical center, meconium was collected from 101 newborn infants (40 with the diagnosis of PPHN based on clinical or echocardiographic criteria and 61 randomly selected, healthy, term infants [control]) and analyzed for NSAIDs (ibuprofen, naproxen, indomethacin, and aspirin) by gas chromatography/mass spectrometry. The risk of developing PPHN was determined in infants 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 group (n = 61). However, the incidence of low Apgar scores (</=6) at 1 minute and 5 minutes was significantly higher in the PPHN group than in the control group. The diagnoses associated with PPHN were primary PPHN (25%), meconium aspiration syndrome (35%), respiratory distress syndrome (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. Fourteen of the 19 infants who were treated with NO (74%) required extracorporeal membrane oxygenation, and 2 died. The overall incidence of positive NSAID in meconium in the study population (n = 101) was 49.5%: 22.8% were positive for ibuprofen, 18.8% for naproxen, 7.9% for indomethacin, and 43.6% for aspirin. There was poor agreement (Cohen's kappa = 0.09) between maternal history of NSAID use and NSAID detection in meconium. PPHN was significantly associated with 1) the presence of at least 1 NSAID in meconium (odds ratio [OR] = 21.47; 95% confidence interval [CI] = 7.12-64.71) or 2) the presence in meconium of aspirin (OR = 8.09; 95% CI = 3.27-20.10), ibuprofen (OR = 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 the antenatal exposure to aspirin, naproxen, and ibuprofen were significantly associated with PPHN and treatment with inhaled NO or extracorporeal membrane oxygenation.
CONCLUSION: We confirm by meconium analysis the results of previous studies that demonstrated that the use of NSAIDs during pregnancy, particularly aspirin, ibuprofen, and naproxen, is high; is grossly underestimated by maternal history; and is significantly associated with PPHN. Thus, the easy access 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 effectively promoted.
Author List
Alano MA, Ngougmna E, Ostrea EM Jr, Konduri GGAuthor
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anti-Inflammatory Agents, Non-SteroidalAspirin
Bronchodilator Agents
Extracorporeal Membrane Oxygenation
Female
Gas Chromatography-Mass Spectrometry
Humans
Ibuprofen
Infant, Newborn
Logistic Models
Meconium
Naproxen
Nitric Oxide
Persistent Fetal Circulation Syndrome
Pregnancy
Prenatal Exposure Delayed Effects
Risk
