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Cyclo-oxygenase (COX) inhibitors for treating preterm labour

Overview of attention for article published in Cochrane database of systematic reviews, June 2015
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Title
Cyclo-oxygenase (COX) inhibitors for treating preterm labour
Published in
Cochrane database of systematic reviews, June 2015
DOI 10.1002/14651858.cd001992.pub3
Pubmed ID
Authors

Hanna E Reinebrant, Cynthia Pileggi-Castro, Carla LT Romero, Rafaela AN dos Santos, Sailesh Kumar, João Paulo Souza, Vicki Flenady

Abstract

Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and appear to have few maternal side effects. However, adverse effects have been reported in the fetus and newborn as a result of exposure to COX inhibitors. To assess the effects on maternal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (24 August 2014). We also contacted recognised experts and searched reference lists of retrieved studies. All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. Two review authors independently evaluated methodological quality and extracted data. We sought additional information from study authors. Results are presented using risk ratio (RR; dichotomous data) and mean difference (MD; continuous data) with 95% confidence interval (CI). The number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated for statistically different categorical outcomes. With the addition of seven studies with a total of 684 women, this review now includes outcome data from 20 studies including 1509 women. The non-selective COX inhibitor indomethacin was used in 15 studies. The overall quality of the included studies was considered moderate to low.Three small studies (102 women), two of which were conducted in the 1980's, compared COX inhibition (indomethacin only) with placebo. No difference was shown in birth less than 48 hours after trial entry (average RR 0.20, 95% CI 0.03 to 1.28; two studies with 70 women). Indomethacin resulted in a reduction in preterm birth (before completion of 37 weeks of gestation) in one small study (36 women) (RR 0.21, 95% CI 0.07 to 0.62; NNTB 2, 95% CI 2 to 4); and an increase in gestational age at birth (average MD 3.59 weeks, 95% CI 0.65 to 6.52; two studies with 66 women) and birthweight (MD 716.34 g, 95% CI 425.52 to 1007.16; two studies with 67 infants). No difference was shown in measures of neonatal morbidity or neonatal mortality.Compared with betamimetics, COX inhibitors resulted in a reduction in birth less than 48 hours after trial entry (RR 0.27, 95% CI 0.08 to 0.96; NNTB 7, 95% CI 6 to 120; two studies with 100 women) and preterm birth (before completion of 37 weeks of gestation) (RR 0.53, 95% CI 0.28 to 0.99; NNTB 6, 95% CI 4 to 236; two studies with 80 women) although no benefit was shown in terms of neonatal morbidity or mortality. COX inhibition was also associated with fewer maternal adverse affects compared with betamimetics (RR 0.19, 95% CI 0.11 to 0.31; NNTB 3, 95% CI 2 to 3; five studies with 248 women) and maternal adverse effects requiring cessation of treatment (average RR 0.09, 95% CI 0.02 to 0.49; NNTB 5, CI 95% 5 to 9; three studies with 166 women).No differences were shown when comparing COX inhibitors with magnesium sulphate (MgSO4) (seven studies with 792 women) or calcium channel blockers (CCBs) (two studies with 230 women) in terms of prolonging pregnancy or for any fetal/neonatal outcomes. There were also no differences in very preterm birth (before completion of 34 weeks of gestation) and no maternal deaths occurred in the one study that reported on this outcome. However COX inhibitors resulted in fewer maternal adverse affects when compared with MgSO4 (RR 0.39, 95% CI 0.25 to 0.62; NNTB 11, 95% CI 9 to 17; five studies with 635 women).A comparison of non-selective COX inhibitors versus any COX-2 inhibitor (two studies with 54 women) did not demonstrate any differences in maternal, fetal or neonatal outcomes.No data were available to assess COX inhibitors compared with oxytocin receptor antagonists (ORAs). Further, no data were available on extremely preterm birth (before 28 weeks of gestation), longer-term infant outcomes or costs. In this review, no clear benefit for COX inhibitors was shown over placebo or any other tocolytic agents. While some benefit was demonstrated in terms of postponement of birth for COX inhibitors over placebo and betamimetics and also maternal adverse effects over betamimetics and MgSO4, due to the limitations of small numbers, minimal data on safety, lack of longer-term outcomes and generally low quality of the studies included in this review, we conclude that there is insufficient evidence on which to base decisions about the role of COX inhibition for women in preterm labour. Further well-designed tocolytic studies are required to determine short- and longer-term infant benefit of COX inhibitors over placebo and other tocolytics, particularly CCBs and ORAs. Another important focus for future studies is identifying whether COX-2 inhibitors are superior to non-selective COX inhibitors. All future studies on tocolytics for women in preterm labour should assess longer-term effects into early childhood and also costs.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 181 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Ethiopia 1 <1%
Netherlands 1 <1%
South Africa 1 <1%
Unknown 178 98%

Demographic breakdown

Readers by professional status Count As %
Student > Master 31 17%
Student > Ph. D. Student 27 15%
Researcher 21 12%
Student > Bachelor 20 11%
Student > Postgraduate 14 8%
Other 39 22%
Unknown 29 16%
Readers by discipline Count As %
Medicine and Dentistry 83 46%
Nursing and Health Professions 22 12%
Pharmacology, Toxicology and Pharmaceutical Science 11 6%
Psychology 7 4%
Social Sciences 5 3%
Other 23 13%
Unknown 30 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 November 2018.
All research outputs
#8,303,067
of 13,777,184 outputs
Outputs from Cochrane database of systematic reviews
#8,853
of 10,744 outputs
Outputs of similar age
#162,476
of 339,475 outputs
Outputs of similar age from Cochrane database of systematic reviews
#153
of 186 outputs
Altmetric has tracked 13,777,184 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 10,744 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.3. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 339,475 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 186 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.