Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor

Besinger, Richard E.; Niebyl, Jennifer R.; Keyes, William G.; Johnson, Timothy R.B.

doi:10.1016/0002-9378(91)90569-d

Cited by 136 publications

(48 citation statements)

References 15 publications

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“…Although clinically evident infection is a contraindication for tocolysis, there is subclinical, histologic evidence of inflammation or inflammatory changes in gestational tissues in over half of deliveries prior to 32-wk gestation (1). Perhaps because of their antiinflammatory properties as well as their inhibition of prostaglandins, nonsteroidal drugs appear to be effective agents for the treatment of idiopathic preterm labor (50,51). However, their use is severely limited by untoward fetal effects (52,53).…”

Section: Discussionmentioning

confidence: 99%

Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

et al. 1995

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Maternal infection is a cause of spontaneous abortion and preterm labor in humans, but the pathophysiology is unclear. We hypothesized that eicosanoids play an important role in infection-driven pregnancy loss. To investigate this hypothesis, we administered lipopolysaccharide (LPS) to pregnant C3H/HeN mice and found that LPS administration caused fetal death in a dose-dependent fashion. Pretreatment with indomethacin significantly decreased the proportion of fetal death from 83% to < 25% in mice injected with 10 jag of LPS. Also, decidual explants from LPStreated mice produced significantly more inflammatory eicosanoids, including prostaglandins E2 and F2. and thromboxane B2, than controls. We investigated the regulatory mechanisms responsible for increased decidual prostanoid production in response to LPS. Western and Northern blots demonstrated that decidual protein and mRNA levels of a recently recognized highly inducible form of cyclooxygenase, COX-2, were substantially increased in mice treated with LPS. Induction of COX-2 was rapid: mRNA was detected 30 min after LPS injection. In contrast, another form of cyclooxygenase, COX-1, was only minimally induced in response to LPS. Our data indicate that LPS induces decidual prostanoid production via increased COX-2 expression. Since LPS-mediated fetal death is markedly diminished by pretreatment with indomethacin, COX-2-mediated eicosanoid production is likely a key pathophysiologic event in LPS-mediated fetal death. (J. Clin. Invest. 1995. 95:725-731.)

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Section: Discussionmentioning

confidence: 99%

Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

et al. 1995

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“…[595][596][597][598][599][600][601][602][603][604][605][606][607] A further three RCTs were added when the searches were updated and expanded to include all NSAIDs. [608][609][610] The quality of the studies included in the review and of the additional studies was generally high (Figure 215).…”

Section: Figure 179 Forest Plot Of the Effects Of Betamimetics Versusmentioning

confidence: 99%

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

Honest

Ca²,

Durée³

et al. 2009

Health Technol Assess

185

146

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For primary prevention, an effective, affordable and safe intervention applied to all mothers without preceding testing is likely to be the most cost-effective approach in asymptomatic women in early pregnancy. For secondary prevention among women at risk of preterm labour in later pregnancy, a management strategy based on the results of testing is likely to be more cost-effective. Implementation of a treat-all strategy with simple interventions, such as fish oils, would be premature for asymptomatic women. Universal provision of high-quality ultrasound machines in labour wards is more strongly indicated for predicting spontaneous preterm birth among symptomatic women than direct management, although staffing issues and the feasibility and acceptability to mothers and health providers of such strategies need to be explored. Further research should include investigations of low-cost and effective tests and treatments to reduce and delay spontaneous preterm birth and reduce the risk of perinatal mortality arising from preterm birth.

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“…Administration of nonsteroidal antiinflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis, have been shown to curtail the progression of both term labor and PTL (16,(92)(93)(94). Currently used NSAIDs, such as indomethacin, block COX-1 and COX-2.…”

Section: Nonsteroidal Anti-inflammatory Drugs As Therapeuticsmentioning

confidence: 99%

“…Currently used NSAIDs, such as indomethacin, block COX-1 and COX-2. Treatment with these drugs is associated with fetal and maternal side effects that have precluded their use (92,95). The efficacy of NSAIDs that inhibit a single COX isoform and their associated side effects were studied in mice as a potential remedy to these problems (96).…”

Section: Nonsteroidal Anti-inflammatory Drugs As Therapeuticsmentioning

confidence: 99%

Insights Into Parturition Biology From Genetically Altered Mice

Ratajczak

Muglia

2008

Pediatr Res

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ABSTRACT:With the growing frequency of preterm birth, increased effort has been made to elucidate the physiology of normal and aberrant parturition. As with many developmental processes, the study of genetically altered mice has led to an increased understanding of mechanisms controlling the maintenance and resolution of pregnancy. Studies in genetically altered mice have implicated critical roles for both prostaglandin synthesis and degradation in luteolysis and the progression of labor. The importance of local modulation of progesterone activity to cervical ripening has also been demonstrated. Although a decline in levels of serum progesterone is a part of normal labor initiation in mice but not humans, murine labor without progesterone withdrawal has been reported in some cases. These findings emphasize the importance of other components of the parturition cascade that are shared in mice and humans and highlights the importance of an increased understanding of the physiology of mouse parturition. (Pediatr Res 64: 581-589, 2008) P arturition is the culmination of mammalian reproduction, a task essential for survival of the species. After a period of uterine quiescence to allow fetal growth and development, changes occur in myometrial contractility that result in efficient expulsion of the fetus. These events have likely evolved to enhance survival of both the fetus and the mother. The nature of these pathways, however, is at best incompletely defined.Increased knowledge of the cascade of events that occur at parturition may lead to advances in combating preterm labor (PTL) or optimization of protocols for medically induced labor. As preterm birth is associated with both increased risk of neonatal mortality and chronic sequelae such as respiratory illness, cerebral palsy, and vision and hearing impairment, it is a major public health concern (1). In the United States, 12.7% of births are preterm (2). Although approximately 50% of preterm births are idiopathic (3), genetic factors seem to be important. Women whose mothers or sisters delivered preterm are at increased risk for premature labor (4,5), indicating a genetic component in the timing of labor. In addition, a study of a Utah population indicates greater genetic relatedness between families with preterm deliveries than control families (6). Because the population studied was descended from the people who established Mormonism in Utah and Mormons have low rates of substance abuse and sexually transmitted diseases, the population used in this study may represent individuals with few environmental risk factors for PTL (6). These studies highlight a role for genetic, and not just environmental factors in predisposition to PTL and serves as a call to researchers to identify and study genes important for parturition.The mouse is a useful research tool for dissecting genetic factors involved in developmental processes. Mice are tractable to genetic manipulation, resulting in an array of available and potential knockout and transgenic mice suitable for studying t...

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Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor

Cited by 136 publications

References 15 publications

Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

Bacterial lipopolysaccharide-mediated fetal death. Production of a newly recognized form of inducible cyclooxygenase (COX-2) in murine decidua in response to lipopolysaccharide.

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

Insights Into Parturition Biology From Genetically Altered Mice

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