Serial salivary estriol to detect an increased risk of preterm birth.

OBJECTIVE: To evaluate serial measurements of salivary estriol (E3) to detect increased risk of spontaneous preterm labor and preterm birth. METHODS: A masked, prospective, multicenter trial of 956 women with singleton pregnancies was completed at eight United States medical centers. Saliva was collected weekly, beginning at the 22nd week of gestation until birth, and tested for unconjugated E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and low-risk groups using the Creasy scoring system. RESULTS: A single, positive (at or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous preterm labor and delivery in the total population (relative risk [RR] 4.0, P <.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk population (RR 3.4, P =.05). Two consecutive positive tests significantly increased the RR in all study groups, with a dramatic improvement in test specificity and positive predictive value but only a modest decrease in sensitivity. In women who presented with symptomatic preterm labor, salivary E3 identified 61% of those who delivered within 2 weeks, using a threshold of 1.4 ng/mL. CONCLUSION: Elevated salivary E3 is associated with increased risk of preterm birth in asymptomatic women and symptomatic women who present for evaluation of preterm labor.

A competency based approach to comprehensive pregnancy care.

This paper assesses the quality and cost of a pregnancy care program based on explicit and achieved patient competencies. By using the USPHS Content of Prenatal Care (1989), key psychosocial/education elements of perinatal care were identified. The goal was a process of patient education that is competency based, integrated, and outcome oriented. Psychosocial assessment, patient education tools, criterion-based length of postpartum stay, and home nursing follow-up were implemented as part of a Comprehensive Pregnancy Program (CPP). Case-control and cohort survey methodology were used to evaluate outcome. There was a significant decrease in hospital length of stay for mothers and newborns after implementation of the CPP. Post-discharge maternal emergency room visits and/or readmits did not increase. Differences in newborn emergency room visits and/or readmits were non-significant. There was a marked reduction in hospital costs for mothers and newborns. Patient satisfaction remained high. Core competencies forming the basis of educational and assessment programs allow the focus of care to be optimal outcome, and provide a useful template against which to measure prenatal, intrapartum, and postpartum care.

Predicting preterm birth: a cost-effectiveness analysis.

OBJECTIVE: The objective of this study was to compare the cost-effectiveness of 9 strategies for the management of threatened preterm labor. STUDY DESIGN: We derived 6 management options from the literature. These were (1) to treat all women with tocolytics and corticosteroids ("treat all"); (2) to treat all women while awaiting results of the "traditional" fetal fibronectin test results, then discontinue treatment on those with negative results; (3) to treat only those with abnormal cervical length measurements as detected by ultrasonography; (4) to treat only those with abnormal "rapid" fetal fibronectin test results; (5) to perform rapid fetal fibronectin testing and cervical length measurements and treat those with a positive result on either or both; (6) not to treat any women ("treat none"). To assess the contributions of tocolytics and corticosteroids to our outcomes, we analyzed 3 additional treatment options: (7) to treat all women with outpatient corticosteroids but not give tocolytics, (8) to administer corticosteroids to all but give tocolytics only to those with abnormal rapid fetal fibronectin test results, and (9) to administer corticosteroids to all but give tocolytics only to those with abnormal cervical length. We used decision analytic techniques to perform a cost-effectiveness analysis. RESULTS: A decision tree was constructed on the basis of these strategies. We reviewed the literature to derive all probability information. We derived sensitivity and specificity for delivery <37 weeks for fetal fibronectin and for abnormal cervical length. Outcomes of interest were respiratory distress syndrome and neonatal death. We derived cost variables from institutional statistics and from values quoted in the literature. Total costs, cases of respiratory distress syndrome, neonatal deaths, and cost-effectiveness ratios were calculated for each of the strategies. We conducted sensitivity analyses on all variables. Universal administration of outpatient corticosteroids was the least expensive option, but it resulted in more cases of respiratory distress syndrome and deaths than "treat all." Rapid fetal fibronectin plus corticosteroids, traditional fetal fibronectin, and cervical length plus corticosteroids were the next least expensive options and resulted in numbers of cases of respiratory distress syndrome and deaths that were similar to those in the "treat all" strategy. The "rapid" fetal fibronectin test, cervical length measurement, rapid fetal fibronectin test plus cervical length measurement, and "treat none" strategies resulted in more respiratory distress syndrome, more deaths, and higher costs. Treating all patients resulted in the fewest number of cases of respiratory distress syndrome and deaths but the greatest costs. CONCLUSION: Risk prediction strategies with the fetal fibronectin assay or corticosteroids plus rapid fetal fibronectin testing or cervical length assessment may offer cost savings compared with treatment of all women with threatened preterm labor and may prevent similar numbers of cases of respiratory distress syndrome and neonatal deaths.

How to diagnose preterm labor: a clinical dilemma.

The clinician is faced with many dilemmas in the diagnosis of preterm labor. The tools at hand (no pun intended) yield subjective information and it is difficult to distinguish true labor from false labor. Because preterm labor is multifactorial in cause and can occur in primiparas, estimating risk for the individual patient is difficult. The cause of the preterm labor in the majority of patients is idiopathic; in this group, the use of salivary estriol as a biochemical marker for preterm labor can increase the accuracy of the diagnosis of true labor. It may also lend confidence to the diagnosis of false labor and may allay anxiety and prevent unnecessary interventions. On the horizon are two noninvasive methods: the EMG, to evaluate uterine contractility, and the collascope, to evaluate the cervix. Both show promise and may provide a more objective assessment of risk for preterm delivery among women with symptoms of preterm labor.

Tympanic versus rectal thermometry in pregnant women.

OBJECTIVE: To assess the accuracy of the tympanic membrane thermometer for use with pregnant women. DESIGN: Cross-sectional descriptive study. SETTING: A major medical center in the midwestern United States. PARTICIPANTS: Thirty-three hospitalized, afebrile pregnant women. MAIN OUTCOME MEASURES: Tympanic membrane thermometers and glass mercury thermometers were used to measure body temperature at the ear and rectum, respectively. The results were compared using two statistical methods: the Pearson correlation coefficient and a new technique suggested by Bland and Altman (1986). RESULTS: Auditory canal temperature measured by a tympanic membrane thermometer correlated with rectal temperature as measured by a glass mercury thermometer (r = 0.38, p = 0.01). Thus, the tympanic membrane thermometer is acceptable for monitoring the body temperature of pregnant women. However, the device's estimation of rectal temperature is not clinically reliable. CONCLUSIONS: Tympanic membrane thermometers, when applied with direct measures, are acceptable for use with pregnant women. It is not recommended that the rectal estimate mode be used with pregnant women.

A multicenter evaluation of intramuscular ritodrine hydrochloride as initial parenteral therapy for preterm labor management.

Ninety-four patients in documented preterm labor received three intramuscular injections of ritodrine hydrochloride over an interval of 6 hours. They subsequently received the tocolytic agent intravenously for a minimum of 6 hours. The effects of ritodrine on uterine activity and the cardiovascular system were determined. Intramuscular ritodrine hydrochloride elicited a prompt and sustained reduction in the frequency of uterine contractions. The transition to intravenous treatment was achieved without an increase in uterine activity. Seventy percent of the patients had a sustained interval of uterine quiescence, and 96% had at least a 24-hour delay in delivery. Initial parenteral therapy with intramuscular ritodrine hydrochloride is safe and effective and may provide an alternative to intravenous therapy and a means of managing preterm labor during interhospital transport of a patient.

Cocaine selectively inhibits beta-adrenergic receptor binding in pregnant human myometrium.

OBJECTIVE: This study evaluated the in vitro effects of cocaine on the binding characteristics of alpha- and beta-adrenergic receptors from pregnant human myometrium. STUDY DESIGN: By means of membrane fractions from myometrium obtained from 26 women at term undergoing cesarean section, equilibrium binding assays were performed with tritiated dihydroergocryptine for alpha-adrenergic receptors and iodine 125-cyanopindolol for beta-adrenergic receptors. Equilibrium competition curves were determined with and without cocaine. Results were compared by one-way analysis of variance. RESULTS: Cocaine inhibited beta-adrenergic receptor binding (inhibition constant = 132 mumol/L) but had little effect on alpha-adrenergic receptor binding (inhibition constant = 1.63 mmol/L). Benzoylecgonine, a stable metabolite of cocaine, had no effect on binding to either receptor. CONCLUSION: Cocaine selectively inhibits myometrial beta-adrenergic receptor binding. This may alter the contractile equilibrium of the pregnant uterus and could explain, in part, the association of cocaine abuse with premature delivery.

Spontaneous and induced cervical ripening. Natural dilation and effacement process and current cervical ripening techniques.

During gestation, the cervix forms a tight sphincter to ensure the integrity of the pregnancy. Toward the end of the pregnancy, hormone-mediated biochemical changes cause the cervix to ripen and become softer and more pliable to allow passage of the fetus. Failure of the cervix to ripen may result in delayed onset of labor and a prolonged and complicated course, especially if labor is artificially induced. Attempts to induce cervical ripening have involved the use of mechanical methods, estrogen and estrogen precursors, relaxin and prostaglandins. The ideal ripening agent is simple and noninvasive, effective within 24 hours, does not compromise mother or fetus and does not stimulate labor (during the ripening process).

Cocaine blocks extraneuronal uptake of norepinephrine by the pregnant human uterus.

Premature labor is one of the most common complications associated with cocaine abuse during pregnancy. Still, the effect of cocaine on the pregnant uterus is largely unknown. Although inhibition of neuronal uptake is the most important effect of cocaine in most tissues, after mid-pregnancy, the uterus has few functioning adrenergic nerve endings. To determine whether cocaine has any effect on uptake during pregnancy, we evaluated the ability of the term pregnant human uterus to take up [3H]-norepinephrine (9 x 10(-8) mol/L) and the ability of cocaine (10(-6)-10(-8) mol/L) to block this uptake. Because d-propranolol has been shown to block the direct effects of cocaine on the pregnant rabbit uterus, we also evaluated the ability of d-propranolol (2 x 10(-6) mol/L) to block the effect of cocaine on catecholamine uptake. The ability of the Uptake 2 inhibitor hydrocortisone (2 x 10(-5) mol/L) to block catecholamine uptake was also studied. We found that [3H]-norepinephrine was taken up by both the pregnant myometrium and endometrium, and that cocaine blocked this uptake by up to 55% at concentrations as low as 10(-7) mol/L. D-propranolol had no effect on the ability of cocaine to block catecholamine uptake. Hydrocortisone blocked uptake by the endometrium by 15% but did not block uptake by the myometrium. We conclude that the pregnant human uterus at term retains the ability to take up catecholamines and that cocaine blocks this extraneuronal uptake. This may explain, in part, the association of cocaine use with premature labor.

Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length.

Risk assessment for preterm delivery remains difficult, particularly among women with no prior history of preterm birth. We hypothesized that accurate assessment of cervical length by endovaginal ultrasonography could predict preterm delivery risk. A total of 178 patients with singleton gestations and without cervical incompetence were studied with transabdominal ultrasonography and endovaginal ultrasonographic cervical length measurement and manual vaginal examination of cervical length. A total of 113 patients who were evaluated by 30 weeks' gestation (excluding four induced preterm deliveries) were analyzed. Preterm delivery risk was compared between women with cervical lengths equal to or greater than the median and those with cervical lengths less than the median. An endovaginal ultrasonographic cervical measurement less than 39 mm was associated with a significantly increased risk of preterm delivery (25.0% versus 6.7%) and detected 76% of preterm births. Manual examination of cervical effacement detected 71% of preterm births, but transabdominal ultrasonographic measurement of cervical length was not preditive. Endovaginal ultrasonographic cervical measurement predicted increased preterm delivery risk regardless of parity or obstetric history. Endovaginal ultrasonography is a promising method for the prediction of risk of preterm birth. Because it has the potential to be an objective measure of cervical length, endovaginal ultrasonography may be superior to manual digital examination for preterm delivery risk assessment.

Percutaneous umbilical blood sampling and umbilical vein transfusions. Rapid serologic differentiation of fetal blood from maternal blood.

Percutaneous umbilical blood samples (PUBS), obtained under ultrasound guidance, are used for prenatal diagnosis and management of hemolytic disease of the newborn (HDN) and other fetal disorders. Rapid testing at the time of sampling is vital to distinguish fetal from maternal blood. Blood typing was performed by slide technique in the treatment room during 38 procedures on 25 patients. Anti-I was used to test 50 presumed PUBS; venous I-positive maternal blood was tested in parallel. Because anti-I cannot detect fetal blood after umbilical vein transfusion (UVT) of I-positive donor blood, ABO and Rh blood typing reagents were used to test 29 samples when maternal and fetal or donor blood groups differed. Monoclonal reagents were used for optimal detection of weak AB antigens in fetal blood. Avid, chemically modified anti-D was used for Rh typing. Blood typing showed 27 (34%) of 79 samples to be maternal blood. Fetal blood was obtained in 8 of 10 cases investigated for fetal disorder and in 16 cases of potential HDN (anti-D, 5; -CD, 5; -cE, 2; -K, 2; -c; -E). The absence of HDN (antigen-negative fetus) was determined in 4 cases. UVT afforded live birth of 9 of 10 infants with HDN and was not indicated in two cases.

Effect of uncomplicated pregnancy on body water content and distribution in baboons.

Body water content and distribution were estimated before, during, or after 32 pregnancies in baboons. Water content of the various compartments (in liters) correlated with body weight in both nonpregnant and pregnant baboons, and with length of gestation in pregnant baboons. In proportion to body weight (in ml/kg), most water compartments did not change significantly with length of gestation. Mean plasma volume and blood volume were higher during pregnancy than before or after.

Maternal blood pressure and fetal ultrasonography in normal baboon pregnancies.

Pregnancy in baboons is characterized by lower systolic, diastolic, and mean blood pressures than in the nonpregnant state. As pregnancy progresses, diastolic and mean pressures tend to increase whereas systolic pressure remains low. Sonographic measurements of fetal growth follow a sigmoid pattern, but their increase in relation to length of gestation approximates a straight line between 6 and 21 weeks of gestation (23 to 84% of term).

Mechanical responses of the rat uterus, cervix, and bladder to stimulation of hypogastric and pelvic nerves in vivo.

Mechanical activities of the uterus, cervix, and bladder were recorded in vivo in anesthetized rats during electrical stimulation of either the hypogastric or pelvic nerve. Ovariectomized controls and hormone-treated groups were used as well as pregnant and postpartum rats. Stimulation of either hypogastric or pelvic nerve produced voltage- and frequency-dependent contractions of the three organs with no evidence of apparent inhibition. All evoked responses were completely abolished by tetrodotoxin, suggesting that these nerves are common pathways of innervation to the three organs. Atropine abolished uterine and cervical responses to both hypogastric and pelvic nerve stimulation, whereas bladder responses were only partly reduced. Hexamethonium almost totally blocked the evoked responses of the uterus and cervix. Phentolamine partly blocked uterine and cervical responses, and propranolol or physostigmine enhanced uterine and cervical responses to both hypogastric and pelvic nerve stimulation. These results suggest that motor innervation to the rat uterus and cervix is predominantly postganglionic cholinergic, with some alpha- and beta-adrenergic components, and that the bladder is innervated by mainly cholinergic and also noncholinergic nerves. Estrogen and estrogen-plus-progesterone pretreatment significantly increased the responses of uterus and cervix but not bladder. Uterine and cervical responses to either hypogastric or pelvic nerve stimulation were markedly reduced late in pregnancy and reappeared within 7 days after delivery.

A functional and structural study of the innervation of the human uterus.

We characterized the innervation of human myometrial tissues by electrical field stimulation and electron microscopy. Nerve-specific parameters (pulse duration 0.6 msec) were used for electrical field stimulation to selectively activate intrinsic nerves. In specimens from nonpregnant, nonparous women (n = 6), tetrodotoxin (10(-6) mol/L) significantly reduced the response to electrical field stimulation by 70%. Contractions to electrical field stimulation were also inhibited to 60% by atropine (10(-5) mol/L) as well as by guanethidine (10(-5) mol/L) and phentolamine (10(-5) mol/L). Propranolol (10(-5) mol/L) had no detectable effect. We obtained similar results from about 50% of the specimens from nonpregnant, parous women (n = 15). The contractile responses of specimens from the term pregnant uterus (n = 13) to electrical field stimulation were not influenced by tetrodotoxin. Ultrastructurally we found nerve profiles in close proximity to muscle cells. About 30% of nerve varicosities in tissues from nonpregnant, nonparous patients could be classified as adrenergic (small, dense-cored vesicles), 53% as cholinergic (small, agranular vesicles), and about 17% as indeterminant (sometimes large, dense-cored vesicles). However, nerve varicosities were rarely observed in term pregnant specimens. These results indicate the presence of tetrodotoxin-sensitive, excitatory innervation of human myometrium consisting of alpha-adrenergic and cholinergic components. Furthermore, denervation may be nearly complete at term and recovery of innervation occurs at a considerable length of time after delivery.