Inhibition of fetal lung maturation by indomethacin in pregnant rabbits

Bustos, Raúl; Ballejo, Gustavo; Giussi, Gustavo; Torres‐Rosas, Rafael; Isa, Julio C.

doi:10.1515/jpme.1978.6.5.240

Cited by 26 publications

(9 citation statements)

References 15 publications

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“…12 The trend for an increased risk of RDS with recent exposure to antenatal indomethacin can be explained by its known inhibitory effect on surfactant production. 16 The trend for a protective effect on RDS when including studies that controlled for antenatal steroid exposure and gestation at birth suggest that the inhibitory effect on surfactant production may be an acute effect and is probably mitigated by the use of antenatal steroids.…”

Section: Commentsmentioning

confidence: 99%

“…15 The incidence of RDS and BPD may be also increased by the inhibitory effects of indomethacin on surfactant production and its stimulatory effects on proinflammatory mediators in the lung. 16 Despite biological plausibility, clinical studies have not consistently shown that individual adverse neonatal effects are associated with the use of AI except for renal dysfunction. Two recent randomized double blind controlled studies evaluating the effect of AI on neonatal outcomes were aborted due to recruitment problems.…”

Section: Introductionmentioning

confidence: 99%

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Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes

Amin

Sinkin

Glantz

2007

American Journal of Obstetrics and Gynecology

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Objective-To determine if indomethacin used as a tocolytic agent is associated with adverse neonatal outcomes.Study Design-We used published guidelines of the Meta-analysis of Observational Studies in Epidemiology Group (MOOSE) to perform the meta-analysis. The search strategy employed included computerized bibliographic searches of MEDLINE (1966MEDLINE ( -2005, PubMed (1966PubMed ( -2005, abstracts published in Obstetrics and Gynecology (1991-2005), abstracts published in Pediatric Research (1991Research ( -2005 and references of published manuscripts. Study inclusion criteria were publication in English, >30 deliveries <37 weeks' gestation, and meeting diagnostic criteria for individual neonatal outcomes. Exclusion criteria included case reports, case series and multiple publications from the same author. Meta-analysis was performed using random effects model if there were > 2 observational studies for a specific outcome. Eggers test was performed to exclude publication bias. Sensitivity analysis was performed to evaluate the effect of antenatal steroid exposure, gestation and recent antenatal indomethacin exposure (≤ 48 hours duration between the last dose and delivery).Results-Fifteen retrospective cohort studies and 6 case controlled studies met inclusion criteria. Antenatal indomethacin was associated with an increased risk of periventricular leukomalacia (OR 2.0, 95% CI 1.3 -3.1). Recent exposure to antenatal indomethacin was associated with necrotizing enterocolitis (OR 2.2, 95% CI 1.1 -4.2). Antenatal indomethacin was not associated with intraventricular hemorrhage, patent ductus arteriosus, respiratory distress syndrome, bronchopulmonary dysplasia and mortality.Conclusion-Antenatal indomethacin may be associated with an increased risk of periventricular leukomalacia and necrotizing enterocolitis in premature infants and, therefore, should be used judiciously for tocolysis.

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Section: Commentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes

Amin

Sinkin

Glantz

2007

American Journal of Obstetrics and Gynecology

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“…This can be induced by antenatal exposure to PG inhibitors [90,91] . The elevated blood fl ow through an immature pulmonary bed produces vascular remodeling that results in a postnatal increase in pulmonary vascular resistance [92,93] and alterations in alveolar development [94][95][96] . Similar results have been reported using animal models of surgical aortopulmonary grafts.…”

Section: Effects Of Increased Pulmonary Blood Flow On the Pulmonary Vmentioning

confidence: 99%

Patent Ductus Arteriosus and Respiratory Outcome in Premature Infants

2005

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A persistent ductus arteriosus is a common event in preterm infants. The systemic-to-pulmonary shunting that occurs as the pulmonary vascular resistance decreases after birth can have significant cardiovascular and respiratory consequences. Acute pulmonary effects include pulmonary edema and hemorrhage, worsened lung mechanics and deterioration in gas exchange with hypoxemia and hypercapnia. The increased pulmonary blood flow can also produce damage to the capillary endothelium and trigger an inflammatory cascade. This, plus the need for longer and more aggressive mechanical ventilation, can explain the association between patent ductus arteriosus and an increased risk for bronchopulmonary dysplasia in extremely premature infants.

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“…Previous studies have associated CLD with persistent PDA [7,8]. Another plausible mechanism is stimulatory effects of indomethacin on proinflammatory mediators in the lung [5]. A recent Cochrane review reported a trend for an increase incidence of CLD with a prolonged course (more than four doses) of indomethacin compared to a short course of indomethacin [13].…”

mentioning

confidence: 99%

“…The increase risk of chronic lung disease (CLD) is thought to be secondary to its inhibitory effects on surfactant production and stimulatory effects on proinflammatory mediators in the lung [5]. Postnatal indomethacin use is associated with intestinal perforation and acute renal dysfunction in premature infants [2,14].…”

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confidence: 99%

Multiple Courses of Indomethacin and Neonatal Outcomes in Premature Infants

2007

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The objective of this retrospective cohort study was to determine patent ductus arteriosus (PDA) closure rate with multiple short courses (three doses) of postnatal indomethacin and compare neonatal outcomes in infants who received two versus three courses of indomethacin for PDA closure. Infants <34 weeks' gestational age born between January 2000 and December 2004 at the University of Maryland Medical Center and who received two or more short courses of indomethacin were included. Outcome measures were ductal closure rate and neonatal outcomes. Of 61 infants who were identified to have received two or more courses of indomethacin, 26 infants closed their ductus after the second course (response rate, 42%). Of the 35 infants who failed ductal closure after two courses, 11 infants had their ductus ligated and 23 received a third course of indomethacin. Of 23 who received a third course, 10 closed their ductus (response rate, 43%). There was no significant difference in the incidence of chronic lung disease, severe retinopathy of prematurity, necrotizing enterocolitis, renal function, or mortality between infants who received two and those who received three courses of indomethacin. Infants exposed to three courses of indo-methacin had a statistically nonsignificant increased incidence of periventricular leukomalacia (p = 0.08; adjusted odds ratio = 4.8; 95% CI, 0.8-30) and remained in the hospital for a longer duration (p = 0.02) compared to infants exposed to two courses of indomethacin. We conclude that multiple courses of indomethacin may be associated with a ductal closure. However, the requirement for a third course may be associated with an increased risk of periventricular leukomalacia. Indomethacin, a potent inhibitor of prostaglandin synthesis, has been routinely used to treat patent ductus arteriosus (PDA) in premature infants [10,28]. However, approximately 20%-40% of premature infants have residual luminal flow or fail to close after the initial short course (three doses given every 12 h) of indomethacin [4,12,15,28]. If the ductus fails to close after the initial course of indomethacin, surgical ligation of PDA and additional indomethacin treatment are two available options for the management of persistent PDA [20,24]. It is not clear whether surgical ligation or multiple courses of indo-methacin should be the preferred treatment of PDA that fails to close after the initial short course of indomethacin [7,19,25]. The medical literature suggests that additional indomethacin treatment is unlikely to produce ductus closure for premature infants, if there is persistent Doppler evidence of ductal flow within 24 h after completion of the initial short course of indomethacin [17]. Contrary to this limited evidence, a recent survey of Neonatal Fellowship Program Directors in the United States reported that multiple courses of indomethacin, up to three, are commonly used for persistent PDA, after the initial course of indo-methacin [1]. This survey also reported that there is wide variation in the ma...

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Inhibition of fetal lung maturation by indomethacin in pregnant rabbits

Cited by 26 publications

References 15 publications

Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes

Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes

Patent Ductus Arteriosus and Respiratory Outcome in Premature Infants

Multiple Courses of Indomethacin and Neonatal Outcomes in Premature Infants

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