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Evaluation of serum cortisol levels in a relatively large and mature group of ventilated and nonventilated preterm infants with respiratory distress syndrome.

Severity of respiratory distress syndrome (RDS) and mechanical ventilation may affect the endogenous cortisol secretion in preterm infants. The aim of this study was to compare the serum cortisol concentrations of a relatively large and mature group of preterm infants with RDS who are ventilated or nonventilated and control preterm infants without RDS. Infants (group I) of comparable gestational ages without RDS served as controls. Infants with RDS who did not need ventilator support and surfactant therapy were considered to have mild RDS (group II). Those requiring mechanical ventilation and surfactant therapy were considered to have severe RDS (group III). Serum cortisol levels were determined after birth and on day 3 of life. The study groups consisted of 79 preterm infants with gestational ages ranging from 31 to 36 weeks, and birthweights ranging from 1086 to 1685 g. All preterm infants showed high cortisol levels after delivery regardless of respiratory distress (group I, n = 25, 34.1 +/- 10.7 microg/dL; group II, n = 23, 33.6 +/- 12.0 microg/dL; and group III, n = 31, 36.4 +/- 12.3 microg/dL). In group III, the cortisol levels (50.8 +/- 16.8 microg/dL) were higher than in group II (40.4 +/- 10.5 microg/dL) and in controls (22.0 +/- 7.2 microg/dL), and the cortisol levels of controls were lower than in group II on day 3 of life. Although the cortisol levels in severe and mild RDS infants increased significantly from their corresponding levels on day 1, they decreased in controls. The cortisol levels on day 3 of life were not significantly different in infants with poor outcome compared with infants with better outcome. Severity of RDS and mechanical ventilation were related to serum cortisol levels of preterm infants. Our study suggests that large and mature preterm infants who are ventilated and/or more severely ill release more cortisol than those less severely ill.

Birth Weight↗

Low-dose ethanol for inhibition of preterm uterine activity.

Inhibition of preterm labor by tocolytic agents reduces the incidence of preterm birth. Betamimetic drugs are the most widely used tocolytic. However, they are from time to time contraindicated, their administration involves potential risks for mother and fetus, and their tocolytic effect is sometimes insufficient. Ethanol infused in intoxicating doses was the first clinically useful tocolytic agent, but because of its potential risks to the fetus, its use is now infrequent. We have examined the efficacy of ethanol infused at much lower rates, alone or in combination with ritodrine, to inhibit preterm uterine contractions. Fifty-four women between 20 and 36 weeks of gestation participated in the study. In 14, betamimetics were contraindicated and they were given ethanol alone. In 38, ritodrine infusions (0.2 gm/min) had failed to arrest preterm labor and they were then given ethanol with ritodrine (0.2 gm/min) The dose of ethanol was 0.11 gm/kg/hour on the average, which is approximately equivalent to the metabolic rate. Altogether, 64 treatments were given, 14 with ethanol alone and 50 combined with 0.2 gm/min ritodrine. In 81% of the treatments, contractions were suppressed within 15.3 hours on the average. Preterm birth (infant less than 2500 gm) was prevented in 70% of the patients. No adverse effects attributable to ethanol were observed. Treatment with low-dose intravenous infusion of ethanol is a cheap, efficacious, and low-risk method to stop preterm uterine activity and is clinically useful for prevention of preterm birth. Possible mechanism of this effect is discussed.

Drug Therapy, Combination↗

[Application of indirect calorimetry in monitoring feeding of low birth-weight preterm infants].

BACKGROUND: We investigated the practical use of indirect calorimetry for the individual nutritional support of preterm infants in order to answer the question whether it is possible to reliably calculate energy expenditure, fat and carbohydrate oxidation in preterm infants individually by using the results of a timed 6-hour-measurement of oxygen consumption and carbon dioxide production. PATIENTS: Measurements were performed in 20 preterm infants (gestational age 30.2 +/- 0.6 weeks, birth weight 1.09 +/- 0.07; mean +/- SEM) at a mean postnatal age of 25 +/- 4 days and with a body weight of 1.35 +/- 0.06 kg. METHODS: Carbon dioxide production (24 h-VCO2), oxygen consumption (24 h-VO2) and respiratory quotient (24 h-RQ) were measured by indirect calorimetry for 24 hours using the Deltatrac II metabolic monitor (Datex, Helsinki, Finland). Additionally, 6 h-VCO2, 6 h-VO2 and 6 h-RQ were determined by measurement over 6 hours. The patients' energy expenditure, fat and carbohydrate oxidation were calculated from VCO2 and VO2 measured over a 24 hour- and 6 hour-period with or without consideration of urinary nitrogen excretion (NU). RESULTS: If NU was not included in the calculation of energy expenditure, the values differed by maximally 1.1% from the calculations including NU. The correlations between the 24 h-RQ and the calculated 24 h-fat or 24 h-carbohydrate oxidation values were statistically significant (r = -0.99; p = 0.0001 and r = 0.773; p = 0.0002 respectively). However, in individual patients, it was not possible to predict 24 h energy expenditure, fat and carbohydrate oxidation of preterm infants using values determined by 6 h indirect calorimetry. CONCLUSION: The determination of the urine-nitrogen excretion is not necessary for calculation of energy expenditure of preterm infants. It is possible to estimate fat and carbohydrate oxidation of preterm infants by the measured 24 h-RQ, but 6 h indirect calorimetry is not accurate enough for calculating the individual nutritional needs of preterm infants in clinical practice. Indirect calorimetry over 24 h may be helpful in the management of selected patients with nutritional problems.

Calorimetry, Indirect↗

Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis.

BACKGROUND: Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery. We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks' gestation. METHODS: In 624 pregnant women at risk for delivering prematurely, vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks' gestation. We then performed a 2:1 double-blind randomization to treatment with metronidazole and erythromycin (433 women) or placebo (191 women). After treatment, the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time (a mean of 27.6 weeks' gestation). RESULTS: A total of 178 women (29 percent) delivered infants at less than 37 weeks' gestation. Eight women were lost to follow-up. In the remaining population, 110 of the 426 women assigned to metronidazole and erythromycin (26 percent) delivered prematurely, as compared with 68 of the 190 assigned to placebo (36 percent, P = 0.01). However, the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis (rate of preterm delivery, 31 percent with treatment vs. 49 percent with placebo; P = 0.006). Of the 358 women who did not have bacterial vaginosis when initially examined, 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely (P = 0.55). The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery (preterm delivery in the treatment group, 39 percent; and in the placebo group, 57 percent; P = 0.02) and in women who weighed less than 50 kg before pregnancy (preterm delivery in the treatment group, 14 percent; and in the placebo group, 33 percent; P = 0.04). CONCLUSIONS: Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery.

Adult↗

Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.

BACKGROUND: Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence. METHODS: To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation. RESULTS: Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available for 953 women in the metronidazole group and 966 in the placebo group. Preterm delivery occurred in 116 women in the metronidazole group (12.2 percent) and 121 women in the placebo group (12.5 percent) (relative risk, 1.0; 95 percent confidence interval, 0.8 to 1.2). Treatment did not prevent preterm deliveries that resulted from spontaneous labor (5.1 percent in the metronidazole group vs. 5.7 percent in the placebo group) or spontaneous rupture of the membranes (4.2 percent vs. 3.7 percent), nor did it prevent delivery before 32 weeks (2.3 percent vs. 2.7 percent). Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit. CONCLUSIONS: The treatment of asymptomatic bacterial vaginosis in pregnant women does not reduce the occurrence of preterm delivery or other adverse perinatal outcomes.

Adult↗

Previous preterm and small-for-gestational-age births and the subsequent risk of stillbirth.

BACKGROUND: Some causes of stillbirth may also lead to fetuses that are small for gestational age (have a low birth weight with respect to their gestational age) or are delivered preterm (before 37 weeks of gestation). It is not known whether the birth of a previous small-for-gestational-age or preterm infant increases the subsequent risk of stillbirth. METHODS: We assessed the associations between previous adverse outcomes of pregnancy and the risk of stillbirth in a nationwide Swedish study of 410,021 women who delivered first and second consecutive singleton infants between 1983 and 1997. There were 1842 and 1062 stillbirths during the first and second pregnancies, respectively. RESULTS: As compared with women whose first infant was born at term (37 weeks of gestation or more) and was not small for gestational age, women whose first infant was born at term or preterm and was small for gestational age had an increased risk of stillbirth during their second pregnancy. The odds ratios for subsequent stillbirth, after adjustment for covariates known to be associated with an increased risk of stillbirth, were 2.1 (95 percent confidence interval, 1.6 to 2.8) among women with a first infant who was born at term and was small for gestational age, 3.4 (95 percent confidence interval, 2.1 to 5.6) among women with a first infant who was moderately (32 to 36 weeks of gestation) preterm and small for gestational age, and 5.0 (95 percent confidence interval, 2.5 to 9.8) among women with a first infant who was very (before 32 weeks of gestation) preterm and was small for gestational age. The odds ratio for subsequent stillbirth among women with a first stillborn infant was 2.5 (95 percent confidence interval, 1.4 to 4.7), as compared with women whose first infant was not stillborn. The rates of stillbirth in second pregnancies ranged from 2.4 per 1000 births among women whose first infant was born at term and was not small for gestational age to 19.0 per 1000 births among women whose first child was very preterm and was small for gestational age. CONCLUSIONS: Delivery of a previous small-for-gestational-age infant is an important predictor of the subsequent risk of stillbirth, particularly if the infant was delivered preterm.

Adult↗

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.

BACKGROUND: Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. METHODS: We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. RESULTS: Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen. CONCLUSIONS: Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.

17 alpha-Hydroxyprogesterone Caproate↗

Elevations of group II phospholipase A2 concentrations in serum and amniotic fluid in association with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether the elevation of secretory group II phospholipase A(2) concentration in the serum and amniotic fluid in preterm labor is associated with intrauterine inflammation. STUDY DESIGN: Serum and amniotic fluid were collected from women with preterm delivery (<37 weeks' gestation; n = 38) and term delivery (n = 20). Phospholipase activity was measured with a highly sensitive system that was based on reverse-phase high-performance liquid chromatographic separation of 9-anthracenylmethyl derivatives of fatty acids released by phospholipase A(2). The concentrations of immunoreactive isozymes (group I or II) of secretory phospholipase A(2) were assayed with a radioimmunoassay kit with a monoclonal antibody against human pancreatic phospholipase A(2) and splenic IIA phospholipase A(2). Localization of immunoreactive group II phospholipase A(2) in the amniotic membrane was determined by immunostaining visualized with the Vectastain ABC (Vector Laboratories, Inc, Burlingame, Calif) method. RESULTS: Enzymatic activities of phospholipase A(2) in the serum and amniotic fluid specimens obtained from patients in preterm labor with chorioamnionitis were significantly higher than those in specimens from patients in term labor. Significant elevations of phospholipase A(2) activities were observed in patients with preterm labor without histologically evident chorioamnionitis. The activity of phospholipase A(2) was clearly correlated with the concentration of the immunoreactive group II phospholipase A(2). Group II phospholipase A(2) was localized in amniotic cells obtained from patients with a pathologically determined diagnosis of chorioamnionitis. The predictive value for chorioamnionitis of the group II phospholipase A(2) concentration was relatively higher than the predictive values of the concentrations of C-reactive protein and interleukins 6 and 8. CONCLUSION: Significant elevations of group II phospholipase A(2) concentrations were detected in the serum and amniotic fluid of women with preterm labor. Group II phospholipase A(2) concentration may be a useful indicator for preterm labor, and phospholipid metabolism is certainly activated both in preterm labor and in apparent inflammatory diseases.

Amniotic Fluid↗

Abnormality of calcium channel inhibitor released from fetal membranes in preterm labor.

OBJECTIVE: This study was undertaken to test the hypothesis that an inhibitor of uterine contractions acting at the level of the dihydropyridine receptor of the uterine L -type uterine calcium channel is released in greater amounts from fetal membranes before term than at term. STUDY DESIGN: Endogenous calcium channel inhibitor activity was generated with standardized 25-cm2 surface area fetal membrane samples from the following 4 categories of women: preterm in labor, preterm not in labor, term in labor, and term not in labor. The amount of inhibitor in each membrane category was quantified by means of a competitive binding assay. Inhibition of uterine contractions induced by Bay K 8644 (an L -type calcium channel agonist) was used as another test of endogenous calcium channel inhibitor activity released from fetal membranes of all 4 groups of patients. RESULTS: Endogenous calcium channel inhibitor activity was most variable but present in the greatest amount in fetal membranes of women who were preterm not in labor followed by those in women at term not in labor and at term in labor. Fetal membranes from women in preterm labor had the least amount of measured endogenous calcium channel inhibitor activity. Consistent with the competitive binding assay, endogenous calcium channel inhibitor activity from fetal membranes from women who were preterm not in labor, at term not in labor, and at term in labor inhibited Bay K 8644-induced uterine contractions. Fetal membranes from women in preterm labor did not inhibit Bay K 8644-induced contractions. Endogenous calcium channel inhibitor activity was present in the chorion, the decidua, and the placenta, with little activity in the amnion. CONCLUSION: The down-regulation of endogenous calcium channel inhibitor activity with advancing gestation is consistent with a potential role for this inhibitor in maintaining uterine quiescence and in regulating the transition into labor. One possible cause of idiopathic preterm labor may be an abnormally low amount of endogenous calcium channel inhibitor activity in fetal membranes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

The risks of spontaneous preterm delivery and perinatal mortality in relation to size at birth according to fetal versus neonatal growth standards.

OBJECTIVE: The aim of this study was to test the null hypothesis that size at birth relative to fetal or neonatal growth standards is not a significant variable related to the risk of spontaneous preterm delivery. STUDY DESIGN: This was a hospital-based cohort study of consecutive births at a tertiary care perinatal center from January 1, 1985, to December 31, 1996. A total of 37,377 pregnancies met the following inclusion criteria: (1) singleton gestation, (2) 25 to 40 weeks' gestation, and (3) no anomalies. Neonates were divided into 5 birth weight categories according to either fetal (uncorrected for sex) or neonatal (corrected for sex) growth standards, as follows: (1) intrauterine growth restriction, birth weight <3rd percentile; (2) borderline intrauterine growth restriction, birth weight > or = 3rd percentile and <10th percentile; (3) appropriate for gestational age, birth weight from 10th percentile through 90th percentile; (4) borderline large for gestational age, birth weight >90th percentile but < or = 97th percentile, and (5) large for gestational age, birth weight >97th percentile. Logistic regression analysis was used to estimate the independent effect of birth weight category on the risk of preterm delivery after spontaneous onset of labor, with the appropriate-for-gestational-age group serving as a reference. RESULTS: When fetal growth standards were applied, there was a significant increase in the risk of spontaneous preterm delivery when birth weight was outside the appropriate-for-gestational-age range (odds ratios of 2.5, 1.4, 1.2, and 1.9 for intrauterine growth restriction, borderline intrauterine growth restriction, borderline large-for-gestational age, and large-for-gestational-age groups, respectively). In contrast, when neonatal growth standards were applied, the risks of spontaneous preterm delivery in intrauterine growth restriction, borderline intrauterine growth restriction, and large-for-gestational-age groups were significantly lower (odds ratios of 0.5, 0.7, and 0.7 for intrauterine growth restriction, borderline intrauterine growth restriction, and large-for-gestational-age groups, respectively) because of an underestimation in the number of fetuses with abnormal size at birth delivered prematurely. With both fetal and neonatal growth standards there was a 5-to 6-fold greater risk of perinatal death for both preterm and term fetuses with intrauterine growth restriction. CONCLUSION: Fetal growth standards are more appropriate in predicting the impact of birth weight category on the risk of spontaneous preterm delivery than are neonatal growth standards. When fetal standards are applied, the risks of preterm birth in both extreme abnormal birth weight categories (intrauterine growth restriction and large for gestational age) are 2- to 3-fold greater than the risk among appropriate-for-gestational-age infants.

Adult↗

Amniotic fluid matrix metalloproteinase-8 in preterm labor with intact membranes.

OBJECTIVE: Intra-amniotic inflammation is a major determinant of maternal and neonatal outcome in patients with preterm labor. Matrix metalloproteinase-8 is a sensitive marker of inflammation in body fluids. This study was conducted to examine the value of amniotic fluid matrix metalloproteinase-8 determinations in patients with preterm labor and intact membranes. STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 371 patients with preterm labor. Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Amniotic fluid analysis included Gram stain examination, white blood cell count, and matrix metalloproteinase-8 (enzyme-linked immunosorbent assay) determination. Nonparametric statistics were used for analysis. RESULTS: The rate of preterm delivery was 54% (200/371) and that of intra-amniotic infection was 9.2% (34/371). The median amniotic fluid matrix metalloproteinase-8 concentration was more than 50-fold higher in patients with intra-amniotic infection than in patients with no intra-amniotic infection (median, 605.6 ng/mL; range, 0.65-15,000 ng/mL vs median, 10.6 ng/mL; range, <0.06-16,600 ng/mL, respectively; P <.0001). The matrix metalloproteinase-8 amniotic fluid concentrations were significantly higher in patients who delivered preterm than in patients who delivered at term (median, 19.5 ng/mL; range, <0.06-16,600 ng/mL vs median, 2.1 ng/mL; range, <0.06-500 ng/mL, respectively; P <.001). After exclusion of patients with intra-amniotic infection, patients who delivered preterm had a significantly higher median amniotic fluid matrix metalloproteinase-8 than patients who delivered at term (P <.05). An amniotic fluid matrix metalloproteinase-8 level of >30 ng/mL was an independent predictor for the occurrence of neonatal morbidity (odds ratio, 3.4; 95% CI, 1.9-5.8; P <.01). CONCLUSION: Increased amniotic fluid matrix metalloproteinase-8 concentrations identify patients at risk for intra-amniotic infection, impending preterm delivery, and adverse neonatal outcome.

Amniocentesis↗

Follistatin-free activin A is not associated with preterm birth.

OBJECTIVE: The purpose of this study was to determine whether follistatin-free activin A (an inhibin-related protein with rising serum levels before term labor) is associated with spontaneous preterm birth in an outpatient population. STUDY DESIGN: From 10 centers, 2929 women were enrolled in the Preterm Prediction Study. Plasma was isolated from blood samples obtained at 24 and 28 weeks of gestation and stored. A nested case-controlled study was performed; there were 197 women with spontaneous preterm birth before 37 weeks of gestation with 24-week samples and 142 cases with 28-week samples that were matched to an equal number of term control samples from each time point. A follistatin-free activin A enzyme-linked immunosorbent assay was performed, with results interpreted as positive or negative (defined as a value less than the assay limit of sensitivity). A comparison of follistatin-free activin A with other tests that were associated with spontaneous preterm birth (alpha-fetoprotein, alkaline phosphatase, cortisol, granulocyte colony-stimulating factor, fetal fibronectin, and cervical interleukin-6) was also performed. RESULTS: The odds ratio for associated spontaneous preterm birth at <37 weeks of gestation if the follistatin-free activin A result was positive was 1.16 at 24 weeks (95% CI, 0.62-2.17) and 1.39 at 28 weeks (95% CI, 0.68-2.84). A positive follistatin-free activin A result at either 24 or 28 weeks was not associated with a positive test for any of the other laboratory tests, except granulocyte colony-stimulating factor at 28 weeks' gestation. CONCLUSION: Follistatin-free activin A is not associated with spontaneous preterm birth in an asymptomatic outpatient population. Follistatin-free activin A may not be an appropriate screening marker for spontaneous preterm birth in the office setting.

Activins↗

Pharmacokinetics of ionized versus total magnesium in subjects with preterm labor and preeclampsia.

OBJECTIVE: Intravenous magnesium sulfate is widely used in obstetrics for the treatment of both preterm labor and preeclampsia. Although therapeutic levels of total magnesium have been proposed, the levels remain controversial. Because the active form of magnesium is the free or ionized form, it is essential to determine whether ionized magnesium and total magnesium levels are highly correlated in vivo. We sought to examine the correlation between ionized magnesium and total magnesium under basal and therapeutic conditions and to define the initiation and elimination pharmacokinetics of both forms during intravenous magnesium sulfate infusion. STUDY DESIGN: Twenty-four singleton pregnant patients who were candidates for magnesium sulfate were studied (preterm labor, 15; preeclampsia, 9). Serial blood samples were taken before the magnesium sulfate infusion, during the first 4 hours after the initiation of magnesium sulfate infusion and for 4 hours after the discontinuation of the infusion. RESULTS: Baseline levels of total magnesium and ionized magnesium were not different between patients with preterm labor and with preeclampsia. Among patients with preeclampsia, although not patients with preterm labor, the initial apparent volume of distribution was significantly smaller for total magnesium than for ionized magnesium (16,397 +/- 1441 vs 23,856 +/- 2745 mL, respectively; P =.03), and the elimination half-life was greater for total magnesium as compared to ionized magnesium (707 +/- 160 vs 313 +/- 29 minutes;P <.05). Linear regression analysis demonstrated a lack of correlation between ionized magnesium and total magnesium during the pretreatment period and during the steady state infusion for both preterm labor and preeclampsia. CONCLUSION: The measurement of total magnesium may not be adequate for the titration of therapeutic magnesium infusions in patients with preeclampsia or preterm labor because of the lack of correlation between total magnesium and the physiologically active ionized magnesium. Further studies may determine whether the measurement of ionized magnesium is a superior method for following the adequacy and safety of the treatment of preeclampsia and preterm labor.

Adult↗

Decidual relaxins: gene and protein up-regulation in preterm premature rupture of the membranes by complementary DNA arrays and quantitative immunocytochemistry.

OBJECTIVE: This study was undertaken to show both decidual relaxin gene and protein up-regulation in preterm premature rupture of the fetal membranes. STUDY DESIGN: Membranes after preterm premature rupture (n = 4) have been matched in pairs with preterm intact membranes (n = 4). These tissues were from patients without infection, labor, preeclampsia or intrauterine growth restriction, and none of the patients had a latency period of more than 8 hours. The messenger RNAs from these tissues were used on complementary DNA expression arrays; 488 genes were analyzed. Relaxin gene expression was quantitated from the arrays and in additional tissues by Northern analysis. The two relaxin proteins, H1 and H2, in the decidual cells were immunolocalized and quantitated by microdensitometry with the use of specific antisera that were raised to decapeptides over the region of least homologic features. The expression of five other genes that were selected from the arrays were quantitated by Northern analysis. RESULTS: Relaxin gene expression was up-regulated 3.4-fold on the complementary DNA arrays but was not confirmed on Northern analysis. On the other hand, protein analysis for relaxin H1 and H2 in the decidual cells showed them to be significantly up-regulated (P <.0001, for both proteins) in patients with preterm premature rupture of the membranes compared with control subjects. The 20 most highly expressed genes at preterm in tissues without rupture were determined. In addition, analysis of the genes that were up-regulated with preterm rupture of the membranes showed 30 differentially expressed genes. CONCLUSION: Relaxin gene expression in the decidua is up-regulated, and its protein expression is significantly increased with preterm rupture of the fetal membranes.

Apoptosis↗

Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes.

OBJECTIVE: The purpose of this study was to determine whether failure of physiologic transformation of the spiral arteries occurs in patients with preterm premature rupture of membranes (PROM). STUDY DESIGN: A cross-sectional study was designed to examine the histopathologic findings in the placental bed and placenta of patients with preterm PROM, preeclampsia, and normal women at term. Immunohistochemistry with cytokeratin 7 and periodic acid-Schiff (PAS) were used to detect trophoblast and fibrinoid and to diagnose failure of physiologic transformation of the spiral arteries. RESULTS: One hundred thirteen cases met the inclusion criteria, 59 from patients with normal pregnancies, 31 with preterm PROM, and 23 with preeclampsia. The mean number of the spiral arteries with failure of physiologic transformation of the myometrial segment was significantly higher in patients with preterm PROM and preeclampsia than in normal pregnant women at term (P =.006 and P <.0001, respectively). In contrast, the mean number of the spiral arteries with failure of physiologic transformation of the decidual segment of the spiral arteries in the basal plate of the placenta was not significantly different in patients with preterm PROM from that in normal pregnant women (P >.05). Placentas from patients with preterm PROM had a higher frequency of vascular lesions than those from normal pregnant women (P =.02). CONCLUSION: Defective placentation, defined as failure of physiologic transformation of the myometrial segment of the spiral artery, is frequently present in preterm PROM.

Adult↗

beta2-Adrenergic receptor genotype and preterm delivery.

OBJECTIVE: Our purpose was to determine whether the functional genetic polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) that result in changes in amino acid residues 16 and 27 are associated with preterm delivery. STUDY DESIGN: A case-control study comparing the distribution of beta(2)AR genotype between 251 Hispanic women delivered at term and 28 Hispanic women delivered preterm. Preterm delivery was defined as spontaneous onset of labor resulting in delivery before 37 weeks of gestation, in a singleton pregnancy, with no apparent etiology for preterm labor and delivery. Genomic DNA was isolated from peripheral blood, and beta( 2)AR alleles were identified by established techniques. RESULTS: Only one woman (4%) with preterm labor was homozygous for Arg16 versus 79 (31%) in the control group (P =.01, odds ratio 0.08). There was no association of preterm labor with genotype at position 27. CONCLUSION: Our data demonstrate that homozygosity for Arg16, which in vitro is associated with decreased down-regulation of the beta(2)AR, protects from preterm delivery.

Adult↗

Assessing the relationship between preterm delivery and various microorganisms recovered from the lower genital tract.

OBJECTIVE: To determine if the likelihood of preterm delivery is more dependent on the specific organisms present in the vagina than on the presence of bacterial vaginosis. METHODS: We evaluated the vaginal fluid of a prospective cohort of women at 23-32 weeks of gestation with signs and symptoms of preterm labor and intact membranes. Forward stepwise logistic regression models were used to evaluate the relationship between preterm delivery and the presence of anaerobic bacteria, Gardnerella, ureaplasmas and mycoplasmas, and sialidase. RESULTS: The cohort included 137 women, and complete delivery information was available for 134 of them. The rate of preterm delivery was 28% (37 of 134). Mycoplasma genitalium independently was associated with spontaneous preterm delivery (OR 3.48; 95% CI 1.41, 8.57). After controlling for this factor, none of the other variables were significantly prognostic for spontaneous preterm delivery (residual overall p = 0.19). CONCLUSION: The presence of Mycoplasma genitalium in the vagina of pregnant women is an independent risk factor for spontaneous preterm delivery.

Adult↗

Fetal fibronectin as a predictor of preterm birth.

Preterm delivery remains the leading cause of perinatal mortality and occurs in approximately 7-9% of pregnancies. The main problem for the obstetrician is the inability to detect women at risk from this complication. The presence of fetal fibronectin (fFN) in cervicovaginal secretions has been proposed as a specific predictor of preterm delivery. Immunohistochemical studies suggest that fFN is present in the extracellular matrix of the decidua basalis next to the intervillus space. It has been studied intensively in symptomatic patients and has a positive predictive value of 43-79%. It has also a negative predictive value of 99.7% for birth within 7 days and 93% for delivery before 37 weeks. Similarly, in high-risk asymptomatic women, it has been proved a useful screening tool for the prediction of preterm delivery, yielding a sensitivity of 43-92%, a specificity of 52-93%, a positive predictive value of 43-85% and a negative predictive value of 86-99%. In low-risk asymptomatic women, fFN has a sensitivity of 63-73%, a specificity of 80-98%, a positive predictive value of 13-36% and a negative predictive value of 95-97%. In women presenting with preterm contractions, a negative test may make one withhold potentially dangerous tocolytic therapy. In asymptomatic women this test can identify patients who have a very high risk for early delivery. Women identified as being high-risk can be offered steroid injections in order to improve lung maturity in preterm babies. Additionally, they can be counselled about the signs and symptoms of preterm labour, so that they can seek medical advice before labour is actually established. However, extensive research is still needed, as no clear benefit in preventing preterm birth using this test, has been shown so far.

Journal Article↗