Indomethacin in Pregnancy: Applications and Safety

Abou-Ghannam, Gael; Usta, Ihab M.; Nassar, Anwar H.

doi:10.1055/s-0031-1284227

Cited by 48 publications

(29 citation statements)

References 151 publications

(268 reference statements)

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“…The effect of indomethacin is attributed to its ability to non-selectively inhibit cyclooxygenase (COX), the precursor enzyme that synthesize PGs (4,5). Despite its effectiveness and minimal side maternal effects; it has a potential to cause a number of complications in foetus and neonate (6,7). The halflife of indomethacin in premature neonates (at least double than in adults) could explain the long-lasting effect of indomethacin after birth (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…Both prenatal and postnatal exposure to indomethacin caused increased neonatal complications including necrotizing enterocolitis (10)(11)(12). Also, it has been shown that indomethacin increased oligohydramnios, intraventricular haemorrhage, renal failure (6). In the kidney, early postnatal indomethacin has been reported to cause long term and adverse effects on renal development and function by disturbance in the renal normal biosynthesis of COX and its metabolites (13).…”

Section: Introductionmentioning

confidence: 99%

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Hepatocellular and developmental influences of early postnatal indomethacin in mice

Nowrouzi¹,

Azadbakht²

2017

BLL

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OBJECTIVES: The effect of early postnatal indomethacin exposure on hepatocellular and developmental alterations in mice liver was investigated. METHODS: Pups received IP injections of 0, 25, 50 and 100 mg/kg indomethacin on P0, then killed at P21 and P60. RESULTS: Indomethacin signifi cantly suppressed body weight at P21, but liver weight signifi cantly decreased only in 25 mg/kg. In contrast, liver weight and liver to body weight ratio signifi cantly increased with increasing dose of indomethacin by P60. The restoration of liver weight was a result of proliferation, as a consequence of a signifi cant increase in the number of uni and bi-nuclear hepatocytes per fi eld in 25 mg/kg at P21 and no evidence of hepatocellular hypertrophy. Indomethacin had a dose-related decrease in number of hepatocytes as the result of hepatocellular hypertrophy confi rmed with hepatocytes presenting large cellular and nuclear size in 50 and 100 mg/kg. Moreover, proliferation contributed to the increased liver size, since bi-nuclear hepatocytes and its ratio increased at P21 at fi rst and then decreased by P60 with increasing in dose. CONCLUSION: Indomethacin has long term effect on liver development in a dose-and time-dependent manner. The hepatocytes during both the liver development and regeneration show signifi cant differences in cell and nuclear number and size (Tab. 3, Fig. 2, Ref. 48). Text in PDF www.elis.sk.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hepatocellular and developmental influences of early postnatal indomethacin in mice

Nowrouzi¹,

Azadbakht²

2017

BLL

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“…Prostaglandin antagonism, such as maternal use of nonsteroidal anti-inflammatory drugs (NSAIDs), can cause fetal closure od the ductus arteriosus.) (12).…”

Section: Discussionmentioning

confidence: 99%

Maternal and Fetal Outcomes in Pregnant Women With Polyhydramnios Treated Based on Maternal and Fetal Distress and Preterm Delivery

Fardiazar¹,

Soltanpour²,

Ghatrehsamani³

2017

International Journal of Women’s Health and Reproduction Scienc

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IntroductionPolyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac which can be seen in 1%-2% of women. The overall prevalence of this condition is reported on 750 pregnancies. Patients suffered from polyhydramnios often referred to hospitals complaining about discomfort in the abdomen and respiratory distress. Abnormal magnitude of the uterus (compared to gestational age) along with difficulty touching embryonic organs and problems associated with fetus auscultation can be observed on physical examination. A definitive diagnosis is ultimately possible through ultrasound and by measuring the ammonic fluid index. Amniotic fluid index (AFI) more than 25 cm is considered as polyhydramnios, accordingly (1).Polyhydramnios may be associated with fetal and maternal complications such as respiratory distress, thromboembolism, preterm labor, atonic uterus, anemia, caesarean section, premature fetus, umbilical cord prolapse caused by the rupture of the membranes and fetal distress (2-4).Common treatment methods of polyhydramnios pregnancies include examination of maternal risk factors (diabetes, viral hepatitis, syphilis and other torch infections and addiction) and examination of fetal risk factors (hydrops fetalis, esophageal atresia, gastroschisis, anencephaly, diaphragmatic hernia, placental chorioangioma, severe anemia, heart problems and chromosomal abnormalities). In mild cases, simple control and follow-ups, continuous ultrasound and conservative treatment methods AbstractObjectives: Polyhydramnios is a condition that could be along with significant maternal, fetal and neonatal consequences. One of the most important complications of this condition is preterm labor and delivery of preterm neonates. Although in mild cases expectant conservative management is effective, in more severe cases, medications (such as indomethacin) and amnioreduction could be considered. Each one of these methods could be accompanied with complications. This study aims to examine the results of management of patients with polyhydramnios according to the fetal and maternal distress and preterm labor criteria. Materials and Methods: In this descriptive-analytic setting, 26 pregnant mothers with polyhydramnios (amniotic fluid index [AFI] more than 30) were managed according to the fetal and maternal distress and preterm labor criteria. In cases under 32 gestational weeks, indomethacin was used with an initial dose of 25 mg every 6 hours and a maximum dose of 2-3 mg/kg that was tapered when the AFI diminished. In refractory cases, the flowchart of fetal and maternal distress and preterm labor was employed. In pregnancies aged over 32 weeks, in case of maternal distress amnioreduction was performed, and in asymptomatic patients, cervical length, funneling, color Doppler and placental thickness were evaluated and in normal cases controlling was carried every 1-2 weeks and abnormal cases amnioreduction was carried out. Results: The mean age of studies patients was 28.12 ± 7.22 years and the mean pregnanc...

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“…Indomethacin is widely used in Canada for acute tocolysis. Although it has been shown to prolong gestation [23], its prolonged use (>48h) has been associated with severe neonatal complications, including premature closure of ductus arteriosus, renal toxicity, necrotizing enterocolitis, intraventricular hemorrhage, and periventricular leukomalacia [24] . It therefore must be used with utmost caution.…”

Section: Indomethacinmentioning

confidence: 99%

Preterm Birth: An Inflammatory Syndrome, Not Just A Myometrial Disorder

Mai-Vo¹,

Nadeau-Vallée²,

Beaudry-Richard³

2017

UOJM

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Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. Although the severity of neonatal outcomes is inversely correlated with gestational age, all PTBs can lead to potentially life-threatening neonatal outcomes and major lifelong health complications. Because advances in neonatal care have substantially decreased neonatal mortality, the incidence of PTB and its complications is unabatedly rising. PTB currently affects more than 10% of births worldwide, with similar numbers in developed countries. Correspondingly, improving neonatal outcome is a key objective of the World Health Organization. The recently approved (in Europe) tocolytics drug, Atosiban, used to prolong preterm gestation, has not been shown to improve neonatal outcome, nor have other tocolytic agents used in clinic. Thus, PTB remains an unmet medical need. Recent evidence shows that most, if not all, PTBs are associated with (overt or occult) inflammatory processes in gestational tissues, independent of infection. Proinflammatory cytokines are produced from maternal and fetal cells in response to sterile or infectious stressors. These seem to orchestrate a multi-tissue response including myometrial contractility, cervical ripening, and weakening/rupture of fetal membranes, leading to the onset of preterm labor. This integrated system might have been conserved through mammalian evolution due to increased maternal and/or fetal survival when gestation is terminated in specific settings, such as infection. Hence, inflammation may be a common pathway to the numerous aetiologies of PTB. Most importantly, recent evidence suggests that inflammation is transmitted to the fetus, thereby inducing organ injuries that may underlie the development of major neonatal diseases. Targeting inflammation prenatally instead of myometrial contraction could be a more successful and safe approach for the management of PTB, as suggested by recent animal studies. ABSTRACTLa naissance prématurée est la principale cause de mortalité et de morbidité néonatale. Bien que la sévérité des issus néonataux soit inversement corrélée avec l'âge gestationnel à la naissance, toutes les naissances prématurées peuvent mener à des issus néonataux potentiellement mortels et à des complications avec répercussions s'échelonnant sur toute la vie. Étant donné que la mortalité néonatale a considérablement diminuée avec les récentes avancées en néonatalogie, l'incidence de la naissance préma-turée et de ses complications sont en hausse. La naissance prématurée affecte présentement plus de 10% des naissances à travers le monde, avec des taux similaires dans les pays développés. Conséquemment, d'améliorer l'issu néonatal est un objectif clé de l'Organisation Mondiale de la Santé. Le tocolytique Atosiban récemment approuvé (en Europe) pour prolonger les gestations pré-maturées n'a pas démontré d'efficacité pour améliorer les issus néonataux, tout comme les autres tocolytiques utilisés en clinique, et la naissance prématurée demeure un besoin médical non-atteint. Des données r...

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Indomethacin in Pregnancy: Applications and Safety

Cited by 48 publications

References 151 publications

Hepatocellular and developmental influences of early postnatal indomethacin in mice

Hepatocellular and developmental influences of early postnatal indomethacin in mice

Maternal and Fetal Outcomes in Pregnant Women With Polyhydramnios Treated Based on Maternal and Fetal Distress and Preterm Delivery

Preterm Birth: An Inflammatory Syndrome, Not Just A Myometrial Disorder

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