Likelihood ratios for the prediction of preterm delivery with biomarkers

Hee, Lene

doi:10.1111/j.1600-0412.2011.01187.x

Cited by 38 publications

(19 citation statements)

References 106 publications

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“…Similarly, it has been noted that for a fixed false positive rate of 10%, maternal characteristics and obstetrical history have a sensitivity of 27.5% for preterm birth with an AUC of 0.61 (0.57–0.65) . This stands in contrast to the results of combined testing with AFP, hCG, estriol, and Inhibin A, which has a LR+ of 5.5 (5.3–5.8) for preterm birth prior to 37 weeks . This study showed that using a high cut‐off threshold for a serum marker substantially enhanced the LR+.…”

Section: Discussionsupporting

confidence: 61%

“…While the prediction of obstetrical risk using maternal serum markers is suboptimal, clinical risk factors used to determine obstetrical risk also fail to meet the standards required for risk/ prognosis setting, as generally an LR + ≥10 is considered to characterize a clinically useful test. 24 For example, a history of prior preterm birth is a commonly recognized risk factor for preterm birth in a subsequent pregnancy, yet this factor only has an LR+ of 3. 24 Similarly, it has been noted that for a fixed false positive rate of 10%, maternal characteristics and obstetrical history have a sensitivity of 27.5% for preterm birth with an AUC of 0.61 (0.57-0.65).…”

Section: Discussionmentioning

confidence: 99%

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Prediction of obstetrical risk using maternal serum markers and clinical risk factors

et al. 2013

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Prediction of obstetrical risk using maternal serum markers and clinical risk factors

et al. 2013

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“…Recently, Conde-Agudelo and colleagues (44) and Hee (45) systematically reviewed the prediction of PTB by various biomarkers, including peripheral, cervicovaginal, and amniotic fluid levels of C-reactive protein (CRP), IL-6, IL-8, TNF-α, IL-2, IL-10, and MMP-8. Only elevated amniotic fluid MMP-8 (likelihood ratio [LR]+ 40) (44) and serum TNF-α (LR+ 10) (45) were associated with substantial increases in the likelihood of PTB. While these findings lend support to the theory that an inflammatory cascade is involved in the initiation of spontaneous preterm labor, several factors prohibit the use of these biomarkers among general clinical populations.…”

Section: The Hypothesismentioning

confidence: 99%

A proposed bio-panel to predict risk for spontaneous preterm birth among African American women

2015

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Preterm birth (PTB), or birth prior to 37 weeks gestation, impacts 11.5% of U.S. deliveries. PTB results in significant morbidity and mortality among affected children and imposes a large societal financial burden. Racial disparities in PTB are alarming. African American women are at more than 1.5 times the risk for PTB than white women. Unfortunately, the medical community’s ability to predict who is at risk for PTB is extremely limited. History of a prior PTB remains the strongest predictor during a singleton gestation. Cervical length and fetal fibronectin measurement are helpful tools. However, usefulness is limited, particularly among the 95% of U.S. women currently pregnant and lacking a history of PTB. Therefore, preventive therapies do not reach a great number of women who may benefit from them. This manuscript, in response to the pressing need for predictors of PTB risk and elimination of racial disparities in PTB, presents a proposed bio-panel for use in predicting risk for spontaneous PTB among African American women. This bio-panel, measured each trimester, includes stimulated production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (Ra), soluble(s) TNF receptor(R) 1, and sTNFR2, and cortisol responsiveness. We hypothesize that greater IL-1β and TNF-α production, decreased IL-1Ra, sTNFR1, and sTNFR2 production, and decreased cortisol responsiveness at each time point as well as a more expedient alignment with this unfavorable profile over time will be associated with PTB. The choice to focus on inflammatory parameters is supported by data highlighting a crucial role for inflammation in labor. Specific inflammatory mediators have been chosen due to their potential importance in preterm labor among African American women. The bio-panel also focuses on inflammatory regulation (i.e., cytokine production upon ex vivo stimulation), which is hypothesized to provide insight into potential in vivo leukocyte responses and potential for initiation of a preterm inflammatory cascade. Production of receptors antagonists is also considered, as pro-inflammatory mediator effects can be greatly influenced by their balance with respective antagonists. Finally, leukocyte responsiveness to cortisol is included as a measure of cortisol’s ability to convey anti-inflammatory signals. The development of a bio-panel predictive of risk for spontaneous PTB among African American women would represent a significant advancement. Available preventive therapies, namely progesterone supplementation, could be delivered to women deemed at risk. Further, the identification of biological predictors of PTB may uncover novel targets for preventive therapies.

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“…Therefore, an accurate diagnostic PTL test, which could stratify the risk, is crucial and would avoid unnecessary hospital admissions and therapies. Multiple tests aiming to identify women at risk of PTB have been proposed . Measurement of the cervical length (CL), fetal fibronectin testing, or a combination of both are useful in determining women at high risk for PTB.…”

Section: Introductionmentioning

confidence: 99%

Cervico‐vaginal placental α‐macroglobulin‐1 combined with cervical length for the prediction of preterm birth in women with threatened preterm labor

Radan

Polowy

Heverhagen

et al. 2019

Acta Obstet Gynecol Scand

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Introduction Preterm birth is a major cause of neonatal morbidity and mortality. There is an urgent need to accurately predict imminent delivery to enable necessary interventions such as tocolytic, glucocorticoid, and magnesium sulfate administration. We aimed to evaluate placental α‐macroglobulin‐1 as a new diagnostic marker in the prediction of preterm birth. Material and methods We performed a prospective observational trial in women with intact membranes between 24+0 and 36+6 weeks of gestation. We included both women with and without threatened preterm labor symptoms. We evaluated the test performance of placental α‐macroglobulin‐1 measurements in cervicovaginal fluid regarding three different presentation‐to‐delivery intervals: ≤2, ≤7, ≤14 days. In addition, we calculated placental α‐macroglobulin‐1 performance in combination with other prognostic factors such as ultrasonographic cervical length measurements. Results We included 126 women in the study. We detected high specificity (97%‐98%) and negative predictive value (89%‐97%) for placental α‐macroglobulin‐1 at all time intervals. We assessed placental α‐macroglobulin‐1 in combination with cervical length measurements (≤15 mm) in the sub‐group of women presenting with threatened preterm labor symptoms (n = 63) and detected high positive predictive values (100%) for 7‐ and 14‐day presentation‐to‐delivery intervals. Conclusions Our study provides evidence that placental α‐macroglobulin‐1 testing in cervicovaginal fluid, in combination with cervical length measurements, accurately predicts preterm birth in women with preterm labor symptoms. This novel test combination may be used clinically to triage women presenting with threatened preterm labor, avoiding overtreatment and unnecessary hospitalizations.

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Likelihood ratios for the prediction of preterm delivery with biomarkers

Abstract: Several biomarkers have been identified for assessment of risk of preterm delivery. Their clinical relevance depends on the efficacy of the interventions which can be offered to these patients.

Cited by 38 publications

References 106 publications

Prediction of obstetrical risk using maternal serum markers and clinical risk factors

Prediction of obstetrical risk using maternal serum markers and clinical risk factors

A proposed bio-panel to predict risk for spontaneous preterm birth among African American women

Cervico‐vaginal placental α‐macroglobulin‐1 combined with cervical length for the prediction of preterm birth in women with threatened preterm labor

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