Serum relaxin as a potential marker for preterm labour.

OBJECTIVE: To determine whether high serum relaxin concentrations in the 30th week of pregnancy were associated with preterm labour. DESIGN: Case-control study. SETTING: Two antenatal clinics of the Department of Obstetrics and Gynecology University Hospital of Aarhus. SUBJECTS: A cohort of 991 women (82% of 1203 eligible) in the 30th week of pregnancy attending one of the two antenatal clinics. The cases comprised 23 (2.4%) women without pre-eclampsia or small for gestational age babies, who were delivered spontaneously before 37 completed weeks gestation. The control group of 46 women was randomly selected from the rest of the cohort, all of them were delivered at term. INTERVENTIONS: Blood samples were collected at 30 weeks gestation and stored for analysis. MAIN OUTCOME MEASURES: Serum relaxin concentrations estimated by ELISA technique, length of gestation at delivery. RESULTS: The mean serum relaxin concentrations in the 30th week of pregnancy was 455 (SD 169) pg/ml and 327 (SD 139) pg/ml in the cases and controls, respectively (P = 0.003, t test). In women with preterm delivery a negative correlation was found between relaxin concentration in the 30th week of pregnancy and the gestational age at parturition (r = -0.53, P = 0.02). CONCLUSION: High relaxin concentrations may be associated with preterm delivery but the present results need confirmation in large scale studies.     

Anemia, ferritin and preterm labor

The results of this study suggest that the additional determination of serum ferritin in pregnancy is necessary for a more reliable classification of iron deficiency. In 300 pregnant women the hematological values (Hb, MCH and serum ferritin) were determined toward the end of gestation. In 36 per cent of the women both Hb values greater than 11 g/dl and MCH values less than 28 pg fail to give evidence of an existing iron deficiency, indicated by serum ferritin values below 20 micrograms/l. The determination of serum ferritin is of particular relevance as a significant correlation was ascertained between low serum ferritin levels and the incidence of preterm labor: 52.3% of the women with serum ferritin levels below 10 micrograms/l and only 9.5% of the women with serum ferritin levels above 20 micrograms/l went into preterm labor. A convincing explanation for this has not yet been found.     

Plasma estradiol as a predictor of preterm labor.

Studies have shown a rapid rise of plasma estradiol-17beta in the maternal circulation before the occurrence of preterm labor. We have attempted to perform a linear regression analysis of the data from normal pregnancies and to set up a 95% upper prediction limit for the normal range of the estradiol level for each week of gestation. The prediction limits were reasonably good, with only five (13%) false negatives. False negatives tend to occur only in late pregnancy.     

Maternal serum ferritin concentration in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the relationship between maternal serum ferritin concentrations in the second trimester and the risk of preterm delivery (PTD). METHODS: A prospective observational study was conducted. Fifty consecutive women with singleton pregnancies, who were admitted to the Maternal Fetal Medicine Unit due to preterm labor in the second trimester, were included. Maternal serum samples for determination of ferritin concentrations were obtained. Multiple logistic regression analysis was performed to control for confounders. RESULTS: Out of fifty patients enrolled in the study, 38% (19/50) delivered prematurely. Eight women (16%) had maternal serum ferritin concentrations above 30 ng/ml in the second trimester. Among them, 75% (n = 6) subsequently presented with preterm delivery (odds ratio (OR) = 6.7 with 95% confidence interval (CI) 1.1-56.2, p = 0.04). Only two patients with increased maternal ferritin concentrations delivered at term. However, 13 patients with second trimester ferritin concentrations below 30 ng/ml had preterm delivery. No significant differences in mean maternal ferritin concentrations were found between patients who delivered preterm and those that delivered at term, 31.9 +/- 50.6 vs. 13.6 +/- 15.2, respectively (p = 0.064). Using a multivariable analysis, controlling for anemia, leucocytosis and maternal age, increased serum ferritin concentrations were found to be an independent risk factor for PTD (OR = 8.6; 95% CI 1.4-52.5; p < 0.019). No significant correlation was found between serum ferritin concentrations and gestational age at birth (Pearson correlation coefficient r = -0.093; p = 0.522). CONCLUSIONS: Maternal ferritin concentrations above 30 ng/ml in the second trimester can serve as a marker for preterm delivery. However, since no correlation was found between serum ferritin concentrations and gestational age at birth, the routine use of serum ferritin as a marker for preterm delivery warrants further investigation.     

Maternal serum advanced glycation end products level as an early marker for predicting preterm labor/PPROM: a prospective preliminary study

Objective: To evaluate the value of maternal serum advanced glycation end products (AGEs) level at 11–13 weeks’ gestation for the prediction of preterm labor and or preterm premature rupture of membranes (PPROM).

Materials and methods: This prospective cross-sectional study is performed in a university-affiliated hospital between February and April 2016. The participants of this study are low-risk pregnant women. Blood samples for maternal AGEs level were collected in the first trimester of pregnancy and all women completed their antenatal follow-up and delivered in our center. During the follow-up 21 women developed preterm labor/PPROM. The first trimester maternal AGEs levels of preterm labor/PPROM cases were compared with uncomplicated cases (n?=?25) matched for age-parity and BMI. The predictive value of AGEs levels for preterm labor/PPROM was also assessed.

Results: First-trimester AGEs levels were significantly higher in cases complicated with preterm labor/PPROM (1832 (415–6682) versus 1276 (466–6445) ng/L, p?=?.001 and 1722 (804–6682) versus 1343 (466–6445) ng/L, p?=?.025). According to receiver-operating characteristic curve analysis, the calculated cut off value of AGEs was 1538?ng/L with the sensitivity 91.7%, specificity 73.8%; and the negative and positive predictive values were 91.6% and 29.5%, respectively.

Conclusions: For the prediction of preterm labor/PPROM, the relatively high AGEs levels in the first trimester might be a useful marker.     

Maternal serum concentration of corticotropin releasing hormone (CRF) as a marker of preterm labor

There is still an urgent need for obstetricians to develop new, noninvasive, accurate methods of diagnosing preterm labor. The purpose of this study was to evaluation of maternal serum corticotropin-releasing factor concentrations and its concentration with onset of labor. The analysis was undertaken of women hospitalized in Research Institute Polish Mother's Memorial Hospital-Clinical of Perinatology (2001-2002) year with pregnancy between 16 to 35 weeks. All pregnancies were singleton gestation free of medical complications but with threatened labor. Maternal peripheral blood samples were obtained from antecubital vein during the first day of hospitalization. The control group consisted of 77 pregnant who delivered term infants whose growth was appropriate for gestational age. The study group consisted of pregnant women who gave preterm delivery. The serum CRF concentrations were measured using EIA method. Maternal serum CRF concentration in control group was 7.28 +/- 1.92 ng/ml. The material was obtained in 26.2 +/- 4.5 week of gestation. CRF concentration in studied group was 6.37 +/- 1.86 ng/ml +/- and the serum was obtained in 24.3 +/- 4.9 ng/ml weeks of gestation. The results were paradoxically significantly higher in control group. CONCLUSIONS: Our results were not in agreement with the findings of other investigators.     

Serum magnesium levels in pregnancy and preterm labor

Pregnancy is marked by a state of hypomagnesemia. The serum magnesium level shows no gestational dependence (mean, 1.79 +/- 0.44 mg/dl) until 33 weeks, at which point it continuously declines. Serum magnesium is not depressed further with the onset of labor at term. Patients in preterm labor have a significantly depressed serum magnesium level (mean, 1.60 +/- 0.46 mg/dl; 21 to 33 weeks; p less than 0.0005). This level was not dependent on whether the etiology for the preterm labor was premature rupture of the membranes (PROM), twin gestation, abruption, placenta previa with bleeding, or chorioamnionitis. With PROM, the serum magnesium level was not depressed prior to the initiation of preterm labor. However, observation of hypomagnesemia for this and other etiologies just prior to the initiation of preterm labor were not available. Possible mechanisms by which hypomagnesemia induces uterine irritability are explored, including inhibition of adenyl cyclase with resultant increase in cytoplasmic calcium levels. Patients with diabetes mellitus appeared to have slightly reduced serum magnesium levels, but the results were not statistically significant. Magnesium levels in patients with preeclampsia were not significantly different from controls. Hypomagnesemia (magnesium 1.4 mg/dl or less) may be a marker for true preterm labor.     

Serial serum ferritin estimation in pregnant women at risk of preterm labor

BACKGROUND: To estimate serial serum ferritin (SF) concentrations after 20 weeks of pregnancy in women at risk of having a preterm labor and to correlate them with the outcome of pregnancy. METHODS: Venous blood samples were drawn serially at 26, 30 and 34 weeks of gestation in one hundred pregnant women who were at risk of having a preterm delivery. Samples were analyzed for hemoglobin (Hb), leukocyte count, hemotocrit serum iron (SI), total iron-binding capacity (TIBC), SF and transferrin saturation. Seventy-six subjects delivered at term and 24 subjects delivered before 37 weeks. The various parameters were compared between the term and the preterm groups. RESULTS: Mean SF at different gestations in the term and the preterm group was not statistically different. Serial SF levels in subjects in the term group showed a declining trend with advancing gestation as seen in normal pregnancies. However, in the preterm group, a rising trend was observed. Further, SF levels of > 30 micro g/dl at 26 weeks and > 40 micro g/dl at 34 weeks were found to have a reasonable sensitivity and specificity for predicting preterm delivery. CONCLUSION: A SF concentration of > 40 micro g/dl and a rise in SF concentration with increasing gestation should alert the clinician regarding the possibility of preterm delivery.     

Serum ferritin levels in preterm infants after multiple blood transfusions

We have examined the effect on iron stores of blood transfusions given to premature neonates during hospitalization in the neonatal intensive care unit as reflected by serum ferritin levels measured for 6 months after discharge. Premature infants who were transfused with more than 100 ml packed cells (group D; n = 11) had higher ferritin levels for a longer period than premature infants who were transfused with smaller volumes (group c; n = 9) or premature and mature infants who were not transfused at all (group B; n = 24 and group A; n = 21, respectively). At 4-5 months the serum ferritin levels in group D (489.8 +/- 132.1 micrograms/L; mean +/- SEM) were significantly higher (P less than 0.001) than those of the other groups. The level of group A term infants (77.5 +/- 12.5 micrograms/L) was higher than those of group B premature infants who did not receive a blood transfusion (33.0 +/- 7.1 micrograms/L) or group C who received less than 100 ml (36.5 +/- 8.8 micrograms/L packed red blood cells. However, these differences were not statistically significant. Our data demonstrate that very-low-birthweight infants who receive a large volume of packed cells during hospitalization may accumulate iron stores sufficient for red cell production during the first 6 months of life. Administration of large amounts of supplemental iron, in such cases, may be curtailed.     

Maternal magnesium level effect on preterm labor treatment

Abstract

Objective: To compare the initial serum magnesium levels between preterm labor (PL) and control groups and to evaluate MgSO4 treatment response in preterm labor group according to their initial serum magnesium levels.

Methods: Hundred women diagnosed as preterm labor between 28 and 33 weeks of gestation and 100 non-complicated pregnant women were enrolled in this prospective study. Total basal serum magnesium levels were measured in both the groups. After a 6?g intravenous bolus of MgSO4, a dose of 2?g/h was given as an infusion in the preterm labor group.

Results: Serum magnesium levels were significantly lower in preterm labor group (p?<?0.001). The active contractions stopped in 69 (73,4%) preterm patients. The basal Mg level was significantly lower in this preterm group (1.6 versus 1.9, respectively, p?<?0.001). Predictive value of basal magnesium level measurement for magnesium tocolysis response was calculated by receiver operating characteristic analyses with 95% confidence interval. Positive predictive and negative predictive values were found as 64.5% and 92.5%, respectively, with 83% accuracy, when cut-off magnesium value was taken as a <1.75?mg/dl (sensitivity?=?80%, specificity?=?84,1%).

Conclusions: Basal magnesium levels in preterm labor had a predictive value in evaluating MgSO4 tocolysis response. It may help to select patients who are appropriate for MgSO4 tocolysis.     

Maternal serum calponin 1 level as a biomarker for the short-term prediction of preterm birth in women with threatened preterm labor

Purpose: To assess the utility of maternal serum calponin 1 level in the prediction of delivery within 7 days among pregnancies complicated with threatened preterm labor.

Materials and methods: Eligible women who presented at 24–34 weeks of gestation with threatened preterm labor underwent sampling for serum calponin 1 level and cervical length measurement. They were followed up until delivery prospectively and the perinatal outcomes of the patients were recorded.

Results: Of 73 women included in the study, 36 women delivered within 7 days and 37 women delivered beyond 7 days after admission. The maternal serum calponin 1 level was significantly high in women who delivered within 7 days (p: 0.031). The threshold value of 2?ng/mL for maternal serum calponin 1 predicted delivery within 7 days with 61.1% sensitivity and 62.2 specificity (area under curve, 0.658, confidence interval 0.53–0.79). The general accuracy values for maternal cervical length measurement (≤25?mm), serum calponin 1 level (>2?ng/mL) and the combination of two tests to predict delivery within 7 days was found to be 64.4%, 61.6% and 72.1%, respectively.

Conclusions: The maternal serum calponin 1 level may be a useful biomarker in short-term prediction of preterm birth among pregnancies complicated with threatened preterm labor, in addition to cervical length measurement.     

Amniotic fluid glucose concentration: a marker for infection in preterm labor and preterm premature rupture of membranes

Amniotic fluid Gram stain and culture have been utilized as laboratory tests of microbial invasion of the amniotic cavity. The Gram stain of amniotic fluid has a low sensitivity in the detection of clinical infection or microbial invasion of the amniotic cavity, and amniotic fluid culture results are not immediately available for management decisions. Glucose concentration is used to diagnose infection in other sites such as cerebrospinal fluid.Objective: The purpose of this study was to evaluate the usefulness of amniotic fluid glucose concentration in detecting microbial invasion of the amniotic cavity associated with preterm labor and preterm premature rupture of membranes.Methods: Amniocentesis was performed in 60 women with preterm labor and/or preterm premature rupture of membranes. Gram stain and culture for Mycoplasma hominis, Ureaplasma urealyticum, aerobic, and anaerobic bacteria were performed. Subjects were studied prospectively for the development of positive amniotic fluid cultures and the development of clinical chorioamnionitis.Results: The diagnosis of clinical chorioamnionitis was made in 25% (15/60) of women entered into the study. Low amniotic fluid glucose concentration Was considered < 15 mg/dl. The sensitivity, specificity, and positive predictive value of low amniotic, fluid glucose concentration to predict clinical chorioamnionitis were 73.3%, 88.1%, and 68.8% respectively, while positive amniotic fluid culture, hada sensitivity of 43.8%, specificity of 79.5%, and positive predictive value of 43.8%.Conclusions: Amniotic fluid glucose concentration was more sensitive in predicting chorioamnionitis than either Gram stain or culture. Amniotic fluid glucose concentration was better in predicting clinical chorioamnionitis than predicting positive amniotic fluid culture results. Gestational age-dependent normal ranges and pathologic conditions that may alter amniotic fluid glucose concentrations should be considered when interpreting amniotic fluid glucose values to diagnose microbial invasion of the amniotic cavity.     

Cervicovaginal fetal fibronectin as a marker for preterm delivery: a meta-analysis.

OBJECTIVE: We performed a meta-analysis to determine the value of cervicovaginal fetal fibronectin as a marker for preterm delivery. STUDY DESIGN: Selection criteria confined the analysis to original, English-language reports of prospective studies including women at <37 weeks' gestation with intact amniotic membranes. For the outcomes of delivery at <37 or <34 weeks' gestation or delivery within 7, 14, 21, or 28 days after fibronectin sampling, we calculated sensitivity and specificity rates for each study, for subgroups of studies, and for all studies combined. RESULTS: A total of 27 studies met our inclusion criteria. For the outcomes of delivery at <37 and <34 weeks' gestation, overall sensitivity rates were 56% and 61% and overall specificity rates were 84% and 83%, respectively. For the outcomes of delivery within 7, 14, 21, and 28 days, we calculated sensitivity rates of 76%, 68%, 61%, and 43% and specificity rates of 88%, 89%, 91%, and 93%, respectively. For the subgroup of patients with symptoms of preterm labor, sensitivity rates for delivery within 7, 14, 21, and 28 days of 89%, 78%, 76%, and 71% and specificity rates of 86%, 86%, 88%, and 83%, respectively, were calculated. CONCLUSION: Among patients with symptoms of preterm labor, cervicovaginal fetal fibronectin appears to be among the most effective predictors of preterm delivery.     

Trends in preterm labor.

Preterm birth has been identified by the National Commission to Prevent Infant Mortality (1988) as the primary cause of the increased infant mortality rate in the United States. An analysis of what is currently known about four areas of preterm labor including (1) definition and causes, (2) identification of patients at risk, (3) management techniques, and (4) use of patient education in labor is presented in this paper. Preterm labor is defined as uterine contractions that occur between 20 and 37 weeks' gestation with progressive cervical dilatation or effacement or both. Directions for future research are discussed.     

Pharmacologic inhibition of preterm labor.

Preterm labor is responsible for a majority of cases of perinatal morbidity and deaths. Prevention of preterm labor is not usually possible; thus pharmacologic treatment is the only recourse available. Numerous agents have been used to treat preterm labor, but none has proved to be superior. This report reviews the current information available about the pharmacology of labor-inhibiting drugs and discusses the clinical approach to the management of preterm labor.