The Preterm Prediction Study: Elevated cervical ferritin levels at 22 to 24 weeks of gestation are associated with spontaneous preterm delivery in asymptomatic women

National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network, USA.
American Journal of Obstetrics and Gynecology (Impact Factor: 4.7). 03/2002; 186(3):458-63. DOI: 10.1067/mob.2002.121088
Source: PubMed


Low serum ferritin levels correlate with low iron stores, whereas high levels are associated with an acute-phase reaction. Our objective was to determine whether elevated levels of ferritin in the genital tract may be a potent marker to identify patients at risk for spontaneous preterm delivery.
We performed a nested case-control study involving 182 women who had spontaneous preterm delivery and 182 term control subjects matched for race, parity, and recruitment center, and selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Development Maternal-Fetal Medicine Units Network. Cervical fluid ferritin was measured by use of radioimmunoassay.
Cervical ferritin levels were significantly higher in women who subsequently had spontaneous early preterm delivery (<32 weeks, mean +/- SD, 37.7 +/- 31.1 vs 21.5 +/- 24.1 ng/mL, P =.002; and <35 weeks, 43.2 +/- 62.7 vs 28.2 +/- 36.7 ng/mL, P =.004) than in term controls. A cervical ferritin of >75th percentile in the controls (>35.5 ng/mL) was found in 52.9% (9/17) of the women delivered <29 weeks vs 17.7% (3/17) of the controls (odds ratio [OR] 5.3 [95% CI 1.1-25.2]) and in 43.5% (20/46) of the women delivered <32 weeks versus 10.9% (5/46) of the controls (OR 6.3, 95% CI 2.1-18.9). Cervical ferritin levels had a weaker association with spontaneous preterm delivery <35 weeks (OR 2.8 [95% CI 1.5-5.1]) and <37 weeks (OR 1.6, 95% CI 1.0-2.5]). Cervical ferritin levels correlated significantly with cervical lactoferrin, interleukin-6 (IL-6), and defensin levels.
Elevated cervical ferritin levels at 22 to 24 weeks of gestation in asymptomatic women are associated with subsequent spontaneous preterm birth. The strong correlation of cervical ferritin with other inflammatory markers provides support for the hypothesis of infection as a mediator of preterm delivery.

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    • "Despite a vast literature review, the evidence in this regard was quite scarce. Consistently with our results, Ramsey et al.,9 found that the mean cervicovaginal ferritin level was higher for those pregnancies ending in a preterm delivery. The predictive values assessed in our study were found to consistently exist both for nulliparrus and multiparous pregnant women. "
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    ABSTRACT: Background: The aim of this study was to determine diagnostic value of cervicovaginal ferretin and serum ferretin levels at midgestation time in predicting preterm delivery in singleton pregnancies. Patients and Methods: A diagnostic test study through a prospective cohort design was carried out on 300 singleton pregnant women in 2012. A blood sample was obtained from all the patients within 22-24 gestational weeks for laboratory assessment of serum ferretin, and cervicovaginal sample was also taken to assess cervicovaginal ferritin level. Ferritin levels were compared between term and preterm deliveries at 37, 34 and 32 weeks of gestation. Receiver operating characteristics (ROC) curves were plotted to assess the diagnostic test values. Results: Mean serum ferritin level was 55.38 [standard deviation (SD 23.8)] ng/mL in term deliveries versus a mean of 91.27 (SD 25.2) ng/mL in preterm deliveries, which showed a statistically significant difference (P < 0.001). The ferritin levels in cervicovaginal term delivery group had mean of 11.29 (SD 16.2) ng/mL compared with a mean of 21.95 (SD 10.1) ng/mL among those with preterm delivery before 37 weeks of gestational age(P < 0.001). The cervicovaginal ferritin level had a moderate to good diagnostic value with an area under curve being above 0.8 for all assessments. The serum ferritin level had a moderate to good diagnostic value with an area under curve being above 0.8 for all assessments. In both tests, its diagnostic value was higher for predicting preterm delivery at earlier gestational age. Conclusions: The results of this study indicate that high levels of serum and cervicovaginal ferritin in singleton pregnancies may alert the clinician of the risk of preterm delivery. Serum and cervicovaginal ferritin measurement at midgestation may be used as a predictive scale for preterm delivery in singleton pregnancies.
    Journal of the Nigeria Medical Association 07/2014; 55(4):321-6. DOI:10.4103/0300-1652.137193
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    ABSTRACT: Occult infection accounts for up to 12% of pregnancy losses following genetic amniocentesis. Elevated serum and cervical fluid levels of ferritin, an acute-phase reactant, have been associated with spontaneous preterm delivery. We determined the association between amniotic fluid (AF) ferritin levels and post-amniocentesis pregnancy loss. We performed a case-control study involving 66 women with a non-anomalous fetus who had a spontaneous pregnancy loss within 30 days following genetic amniocentesis and 66 term controls matched for maternal age, gestational age, time of test and indication for amniocentesis. Amniotic fluid ferritin and interleukin-6 (IL-6) levels were measured using commercially available kits. Mean (+/- SD) AF ferritin levels were similar between the cases (19.3 +/- 21.4 ng/ml) and the controls (19.8 +/- 22.7ng/ml) (p = 0.9). Mean (+/- SD) AF IL-6 levels were significantly higher in the women with post-amniocentesis pregnancy loss (4.0 +/- 13.1 ng/ml) than in controls (0.5 +/- 0.7 ng/ml) (p = 0.04). A significant proportion (12.1%, 8/66) of the women with post-amniocentesis pregnancy loss had elevated amniotic fluid IL-6 levels (> 3 SD, 2.5 ng/ml) indicating inflammation, as compared to none in the control group (p = 0.01). In this subgroup of women with pregnancy loss and elevated IL-6 levels, AF ferritin levels were significantly elevated (52.0 +/- 45.5 ng/ml) compared to the level in women who had a term delivery (19.8 +/- 22.7 ng/ml) (p = 0.002), and were strongly correlated with IL-6 levels among the cases (r = 0.67, p < 0.001). The strong correlation of AF ferritin with IL-6 levels, along with the high ferritin values in cases with high AF IL-6, indicates that ferritin is a marker of inflammation in asymptomatic women destined to have an early pregnancy loss.
    Journal of Maternal-Fetal and Neonatal Medicine 05/2002; 11(5):302-6. DOI:10.1080/jmf.11.5.302.306 · 1.37 Impact Factor
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    ABSTRACT: The Preterm Prediction Study conducted by the Maternal Fetal Medicine Network between 1993 and 1996 studied a large number of risk factors for preterm birth in more than 3,000 women at 10 centers. The goals of the study were to better understand the strength of one risk factor versus another and to explore interactions among the predictors looking for combinations of factors that were more predictive of preterm birth than any single factor used alone. The most potent factors that were associated with spontaneous preterm birth at < 32 weeks were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and < l0th percentile cervical length (odds ratio, 5.8), and in serum, > 90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and > 75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at < 35 weeks were generally similar but not as strong. The overlap among the strongest biologic markers for predicting spontaneous preterm birth was small. This suggests that the use of tests such as maternal alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.
    Seminars in Perinatology 06/2003; 27(3):185-93. DOI:10.1016/S0146-0005(03)00017-X · 2.68 Impact Factor
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