Screening to prevent spontaneouspreterm birth: Systematic reviews of accuracy and effectiveness literature with economic modelling

Birmingham Women's Hospital and Department of Obstetrics and Gynaecology, University of Birmingham, UK.
Health technology assessment (Winchester, England) 09/2009; 13(43):1-627. DOI: 10.3310/hta13430
Source: PubMed


To identify combinations of tests and treatments to predict and prevent spontaneous preterm birth.
Searches were run on the following databases up to September 2005 inclusive: MEDLINE, EMBASE, DARE, the Cochrane Library (CENTRAL and Cochrane Pregnancy and Childbirth Group trials register) and MEDION. We also contacted experts including the Cochrane Pregnancy and Childbirth Group and checked reference lists of review articles and papers that were eligible for inclusion.
Two series of systematic reviews were performed: (1) accuracy of tests for the prediction of spontaneous preterm birth in asymptomatic women in early pregnancy and in women symptomatic with threatened preterm labour in later pregnancy; (2) effectiveness of interventions with potential to reduce cases of spontaneous preterm birth in asymptomatic women in early pregnancy and to reduce spontaneous preterm birth or improve neonatal outcome in women with a viable pregnancy symptomatic of threatened preterm labour. For the health economic evaluation, a model-based analysis incorporated the combined effect of tests and treatments and their cost-effectiveness.
Of the 22 tests reviewed for accuracy, the quality of studies and accuracy of tests was generally poor. Only a few tests had LR+ > 5. In asymptomatic women these were ultrasonographic cervical length measurement and cervicovaginal prolactin and fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks. In this group, tests with LR- < 0.2 were detection of uterine contraction by home uterine monitoring and amniotic fluid C-reactive protein (CRP) measurement. In symptomatic women with threatened preterm labour, tests with LR+ > 5 were absence of fetal breathing movements, cervical length and funnelling, amniotic fluid interleukin-6 (IL-6), serum CRP for predicting birth within 2-7 days of testing, and matrix metalloprotease-9, amniotic fluid IL-6, cervicovaginal fetal fibronectin and cervicovaginal human chorionic gonadotrophin (hCG) for predicting birth before 34 or 37 weeks. In this group, tests with LR- < 0.2 included measurement of cervicovaginal IL-8, cervicovaginal hCG, cervical length measurement, absence of fetal breathing movement, amniotic fluid IL-6 and serum CRP, for predicting birth within 2-7 days of testing, and cervicovaginal fetal fibronectin and amniotic fluid IL-6 for predicting birth before 34 or 37 weeks. The overall quality of the trials included in the 40 interventional topics reviewed for effectiveness was also poor. Antibiotic treatment was generally not beneficial but when used to treat bacterial vaginosis in women with intermediate flora it significantly reduced the incidence of spontaneous preterm birth. Smoking cessation programmes, progesterone, periodontal therapy and fish oil appeared promising as preventative interventions in asymptomatic women. Non-steroidal anti-inflammatory agents were the most effective tocolytic agent for reducing spontaneous preterm birth and prolonging pregnancy in symptomatic women. Antenatal corticosteroids had a beneficial effect on the incidence of respiratory distress syndrome and the risk of intraventricular haemorrhage (28-34 weeks), but the effects of repeat courses were unclear. For asymptomatic women, costs ranged from 1.08 pounds for vitamin C to 1219 pounds for cervical cerclage, whereas costs for symptomatic women were more significant and varied little, ranging from 1645 pounds for nitric oxide donors to 2555 pounds for terbutaline; this was because the cost of hospitalisation was included. The best estimate of additional average cost associated with a case of spontaneous preterm birth was approximately 15,688 pounds for up to 34 weeks and 12,104 pounds for up to 37 weeks. Among symptomatic women there was insufficient evidence to draw firm conclusions for preventing birth at 34 weeks. Hydration given to women testing positive for amniotic fluid IL-6 was the most cost-effective test-treatment combination. Indomethacin given to all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among symptomatic women. For a symptomatic woman, the most cost-effective test-treatment combination for postponing delivery by at least 48 h was the cervical length (15 mm) measurement test with treatment with indomethacin for all those testing positive. This combination was also the most cost-effective option for postponing delivery by at least 7 days. Antibiotic treatment for asymptomatic bacteriuria of all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among asymptomatic women but this does not take into account the potential side effects of antibiotics or issues such as increased resistance.
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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Available from: Sue Jowett, Mar 11, 2014
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    • "CRP, as a marker of preterm labor in symptomatic women[24] with LR + 6.3, and SENS 38% and in asymptomatic women[25] with LR+1.8, and SENS 26%, were noted. Also, CRP (week 34) with LR + 6.8 and LR- 0.7,[24] CRP (week 35) with LR+2.8 and LR- 0.6,[26] and CRP (week 37) with LR + 4.5 and LR- 0.3,[27] were reported in preterm labor prediction. Our results on evaluation of CRP in gestational age of 24 to 34 week showed that CRP with LR + 3.9, LR-0.66, "
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    ABSTRACT: Background: Levels of a number of some biomarkers have been associated with spontaneous preterm birth. This study was aimed to evaluate the relation between C-reactive protein (CRP) with preterm labor and response to tocolytic therapy. Materials and Methods: Seventy five pregnant women with symptoms of preterm labor (cases) in compare with 75 term women (controls) were enrolled. Baseline data and CRP was recorded. So, cases were under treatment tocolysis with the use of magnesium sulfate, and then they were followed till delivery time to assess the response to the treatment. Results: Sixteen patients with symptoms of preterm labor did not response to the treatment and delivered prematurely and 59 women response to tocolytic treatment and delivered at term. The curve constructed cut-off value for >3.6 (AUC, 0.683; SE, 0.041; P < 0.0001) for CRP, indicating a significant relationship with preterm labor. Also, there was significant relationship between CRP level with response to the treatment in cut-off >1.8 (AUC, 0.738; SE, 0.076; P = 0.001) for CRP. Conclusions: Maternal concentrations of CRP can be used as appropriate biomarker for predicting preterm labor and response to tocolytic therapy in pregnant women.
    07/2014; 3:154. DOI:10.4103/2277-9175.137864
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    • "Spontaneous preterm labour is a major public health problem [1]. A recent comprehensive review on the prediction and prevention of preterm birth report concluded that an intervention that is safe and affordable and can be applied to all mothers without preceding testing is likely to be the most cost-effective approach to prevention of preterm birth in women without symptoms [2]. Dietary supplementation with marine oils containing omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have gained attention due to their function in foetal development and the role they play in inflammation [3]. "
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    ABSTRACT: To investigate the effect of omega-3 PUFAs, eicosapentanoic acid (EPA) and docosohexanoic acid (DHA) on inflammatory cytokine production in the amnion. Amnion explants were obtained at elective caesarean sections and cultured in vitro with EPA and DHA. IL-8 and IL-6 secretion was determined by ELISA, the role of PPARγ was investigated using specific agonists and antagonists and activity of MMP assessed by gelatin zymography. A combination of EPA and DHA significantly reduced the concentration of IL-8 and IL-6 released into the supernatant compared to untreated controls (p<0.001). Stimulation of PPARγ with troglitazone reduced IL-8 production, and the PPARγ antagonist GW9662 partially reversed this effect. The activity of MMP-9 was also significantly reduced by treatment with EPA and DHA in combination compared to untreated control (p<0.05). The omega-3 PUFAs EPA and DHA decrease the inflammatory response of the amnion, and this may be partially mediated through PPARγ.
    Prostaglandins Leukotrienes and Essential Fatty Acids 07/2013; 89(4). DOI:10.1016/j.plefa.2013.07.001 · 2.35 Impact Factor
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    • "Preterm labour <34 weeks occurs in about 4% of pregnancies [1]. In 80–85% of cases of spontaneous preterm labour (PTL) <28 weeks, there is evidence of intrauterine infection [2]. "
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    ABSTRACT: Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2) protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ(12,14)-Prostaglandin J(2) (15dPGJ(2)) inhibits nuclear factor Kappa B (NF-κB) in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ(2) could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4) synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs) from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ(2) or vehicle control and stimulated with phorbol myristyl acetate (PMA)/ionomycin. The percentage of CD4(+) cells producing interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ(2) reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2(+ve) cells. 15dPGJ(2) also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ(2) suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.
    Mediators of Inflammation 05/2012; 2012(43):416739. DOI:10.1155/2012/416739 · 3.24 Impact Factor
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