Fetal ear length measurement: a useful predictor of aneuploidy?

OBJECTIVE: To determine the usefulness of short ear length (EL) measurement in the prenatal detection of fetuses with chromosomal abnormalities. DESIGN: Fetal EL measurements, routine biometry and complete anatomic survey for fetal abnormalities were prospectively performed by antenatal sonography. SUBJECTS: One thousand eight hundred and forty-eight patients with singleton pregnancies undergoing genetic amniocentesis in the second or third trimester. METHODS: Complete data for EL, biometry and anatomic survey for major structural abnormalities and minor sonographic markers of chromosomal abnormality were available in 1311 fetuses. Of these, 48 (3.7%) had an abnormal karyotype and 1263 (96.3%) had a normal karyotype. Using an EL measurement of < or = 10th percentile for corresponding gestational age in normal fetuses as abnormal cut-off values, detection rates for chromosomal abnormalities by short EL were determined. RESULTS: Among the 48 abnormal karyotypes, 34 were considered significant, and 11 of these 34 (32.4%) fetuses had short EL. In 14 cases, the karyotypic abnormality was considered non-significant and fetal EL was normal in all cases. Of the 34 fetuses with significant chromosomal abnormalities, six (17.6%) on antenatal sonography had no detectable abnormal findings, other than short EL. An increased biparietal diameter (BPD)/EL ratio of > or = 4.0 was also noted in fetuses with an abnormal karyotype, but the sensitivity and predictive value of increased BPD/EL ratio alone or increased BPD/EL ratio in combination with short EL was no better than the sensitivity and predictive value of short EL alone. A combination of short EL and abnormal ultrasound, however, gave a much higher positive predictive value (46%) for significant chromosomal abnormalities. CONCLUSIONS: Our findings suggest that in women at high risk for fetal chromosomal abnormality, a short fetal EL measurement on prenatal ultrasound, either alone or in combination with other sonographically detectable structural abnormalities, may be a useful parameter in predicting fetal aneuploidy.

Decreased amniotic fluid index in low-risk pregnancy.

OBJECTIVE: To evaluate the perinatal outcomes of pregnancies complicated by isolated decreased amniotic fluid volume (AFI) after 30 weeks' gestation (AFI < or = 5 or > 5 cm but < 2.5th percentile). STUDY DESIGN: We retrospectively studied 150 low-risk singleton pregnancies > 30 weeks' gestation with decreased AFI. We also compared the outcomes of 57 pregnancies with AFI < or = 5 cm to those of 93 pregnancies with AFI > 5 cm but < 2.5th percentile (borderline AFI). Pregnancy outcome was assessed with respect to antepartum, intrapartum and neonatal measures. Statistical significance (P < .05) between groups was determined by means of the Student t test and chi 2 analysis. RESULTS: There were no statistically significant differences between pregnancies with AFI < or = 5 cm and those with AFI > 5 cm but < 2.5th percentile with respect to labor induction for an abnormal nonstress test (7.0% vs. 7.5%, overall 7.3%), cesarean sections for fetal heart rate abnormalities (7.0% vs. 7.5%, overall 7.3%), presence of meconium (16.1% vs. 15.7%, overall 16%) and Apgar score < 7 at five minutes (0 vs. 1.1%, overall 0.66%). There were no perinatal deaths in either group. Antepartum variable decelerations were more common in pregnancies with AFI < or = 5 cm as compared to those with AFI > 5 cm but < 2.5th percentile (63.1% vs. 45.1%, P = .007; overall 53.3%). CONCLUSION: With antepartum monitoring, perinatal outcome in low-risk pregnancies with an isolated decreased AFI after 30 weeks' gestation (< or = 5 or > 5 cm but < 2.5th percentile) appears to be good.

Ultrasonographic ear length measurement in normal second- and third-trimester fetuses.

OBJECTIVE: We sought to develop a nomogram for fetal ear length measurements from a large population of healthy second- and third-trimester fetuses and to investigate the correlation of fetal ear length with other standard fetal biometry measurements, as follows: biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. STUDY DESIGN: Ear length measurement was obtained prospectively in 4240 singleton fetuses between 15 and 40 weeks' gestational age. Either complete data for normal karyotype on amniocentesis or normal infant examination at birth or both were available in 2583 cases. These constituted the final study population. RESULTS: A nomogram was developed by linearly regressing ear length on gestational age (Ear length [in millimeters] = 1.076 x Gestational age [in weeks] - 7. 308). There was a high correlation between ear length and gestational age (r = 0.96; P =.0001). CONCLUSION: The results of this study provide normative data on growth of fetal ear length from 15 to 40 weeks' gestation. Good correlation was also observed between ear length and other fetal biometric measurements (biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length).

Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor.

OBJECTIVE: To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor. METHODS: Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis. RESULTS: Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy. CONCLUSION: Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.

Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial.

The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

Fetal fibronectin as a predictor of preterm birth in patients with symptoms: a multicenter trial.

OBJECTIVE: Our aim was to determine whether the presence of fetal fibronectin in vaginal secretions of patients with symptoms suggestive of preterm labor predicts preterm delivery. STUDY DESIGN: Patients who were examined at the hospital between 24 weeks' and 34 weeks 6 days' gestation with intact membranes, no prior tocolysis, symptoms suggestive of preterm labor, and cervical dilation < 3 cm were recruited at 10 sites. Swabs of the posterior fornix were assayed for the presence of fetal fibronectin by monoclonal antibody assay, with a positive result defined as > or = 50 ng/ml. Results were not available to the managing physicians. Tocolysis was used when clinically indicated after specimen collection. RESULTS: A total of 763 patients had fetal fibronectin results and pregnancy outcome data available for analysis. Fetal fibronectin was detected in specimens from 150 (20%) patients. Compared with patients who had negative results, patients who had positive results for fetal fibronectin were more likely to be delivered within 7 days (relative risk 25.9 [95% confidence interval 7.8 to 86]), within 14 days (relative risk 20.4 [95% confidence interval 8.0 to 53]), and before 37 completed weeks (relative risk 2.9 [95% confidence interval 2.2 to 3.7]). The negative predictive values for delivery within 7 days, within 14 days, and at < 37 weeks were 99.5%, 99.2%, and 84.5%, respectively. When we used multiple logistic regression analysis to control for potential confounding variables among singleton pregnancies, only the presence of fetal fibronectin (odds ratio 48.8, 95% confidence interval 7.4 to 320), prior preterm birth (odds ratio 8.3, 95% confidence interval 1.5 to 46.6), and tocolysis (odds ratio 4.1, 95% confidence interval 1.0 to 16.0) were associated with birth within 7 days; fetal fibronectin (odds ratio 3.6, 95% confidence interval 2.2 to 5.9), prior preterm birth (odds ratio 2.5, 95% confidence interval 1.4 to 4.4), cervical dilatation > 1 cm (odds ratio 2.9, 95% confidence interval 1.6 to 5.2), and tocolysis (odds ratio 4.5, 95% confidence interval 2.8 to 7.2) were all independently associated with delivery before 37 weeks. CONCLUSION: In a population of patients with symptoms, the presence of fetal fibronectin in vaginal secretions best defines a subgroup at increased risk for delivery within 7 days; the high negative predictive value of fetal fibronectin sampling supports less intervention for patients with this result.

Intrathecal sufentanil for labor analgesia--sensory changes, side effects, and fetal heart rate changes.

This study was designed to evaluate intrathecal (IT) sufentanil for labor analgesia with respect to sensory changes, side effects, and fetal heart rate (FHR) changes. In Phase I of the study, data regarding duration of analgesia and hemodynamic changes were obtained retrospectively from the labor and anesthetic records of 90 patients who had received IT sufentanil, 10 micrograms in 1 mL of saline, during active labor. In Phase II, an additional 18 parturients who received similar treatment were studied prospectively to document sensory, motor, and hemodynamic changes, as well as the incidence of side effects. In Phase I, analgesia occurred rapidly and lasted 124 +/- 68 min (SD); 19% of patients required no further analgesia before delivery. In Phase II, median time to onset of analgesia was 3 min (range 1-6 min) and mean duration of analgesia was 96 +/- 36 min. Decreased sensation to pinprick and cold occurred within 6 min extending from T4 to L4 (upper and lower median levels) in the majority of patients. All subjects requested additional analgesia within approximately 30 min of recession of sensory changes. Motor strength remained normal throughout. Hypotension (systolic blood pressure [BP] < or = 90 mm Hg or > 20% decrease in systolic BP) occurred in 14% and 11% of patients in Phase I and II, respectively. Perineal itching preceded analgesia in 95% of patients and all subjects experienced mild sedation. FHR changes occurred in 15% of cases but were not associated with adverse neonatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nicardipine on the reversal of magnesium toxicity by calcium gluconate in nonpregnant rabbits.

OBJECTIVE: To determine whether nicardipine, a dihydropyridine, inhibits the ability of calcium gluconate to reverse magnesium-induced toxicity. METHODS: The reversal of magnesium-induced neuromuscular blockade of skeletal muscle in the presence of nicardipine was assessed using a nerve stimulator. Nicardipine (12 mg) or an equivalent volume of saline was administered intramuscularly to 19 nonpregnant rabbits in a randomized, blinded manner. Magnesium sulfate, 800 mg, was then infused intravenously in all animals, an amount sufficient to cause toxicity as measured by depression of skeletal muscle twitch and by average serum levels of 10.4 mEq/L. Calcium gluconate (300 mg) was then infused in all animals, and reversal of neuromuscular blockade was measured using the nerve stimulator to compare the saline- and nicardipine-treated groups. RESULTS: Administration of calcium gluconate was equally effective in reversing magnesium-induced toxicity in both the control and test groups. CONCLUSION: Nicardipine does not block the ability of calcium gluconate to reverse magnesium-induced neuromuscular blockade.

Application of the hemoglobin alkaline denaturation test to determine the fetal origin of blood: applicability to funipuncture.

In funipuncture, fetal blood is collected by passing a needle transabdominally into an umbilical vessel under ultrasound guidance. The objective of this study was to develop an accurate, inexpensive test that immediately indicates the source of the blood during the umbilical sampling procedure, ie, before the needle is withdrawn. To distinguish fetal from adult blood, we used a modified version of the Apt test, which is based on the different alkaline denaturation properties of adult hemoglobin and fetal hemoglobin. We collected 18 blood samples from adult volunteers and 22 umbilical cord samples from deliveries occurring between 25-42 weeks' gestation. The samples were tested for character and time of color change upon addition of increasing concentrations of NaOH. We found 0.2N NaOH to be the ideal concentration to add to hemolyzed blood samples for a reliable determination of blood origin. All of the hemolysates tested in blinded trials using 0.2N NaOH were correctly identified as fetal or adult. The increase in adult hemoglobin due to the increase in gestational age alters the rate of color change, but the difference was not clinically important because it did not alter the efficacy of the alkaline denaturation test.

Fetal heart rate after epidural lidocaine and bupivacaine for elective cesarean section.

This prospective double-blind study was designed to determine whether the fetal heart rate (FHR) changes that have been reported after epidural administration of bupivacaine and lidocaine during labor are present when larger doses of these drugs are given during elective cesarean section. Prior to inserting an epidural catheter, FHR and maternal vital signs were monitored during a control period in 60 healthy term parturients. Patients were randomly assigned to receive either 0.5% bupivacaine with 0.1 mEq sodium bicarbonate added to each 20 ml (n = 30) or 2% lidocaine with 1:300,000 epinephrine (n = 30). A 3-ml test dose of the study solution was injected via the catheter and was followed by an additional 17 ml, in increments; additional doses were administered as necessary to obtain surgical anesthesia. FHR and maternal vital signs were monitored for at least 20 min and the characteristics of the anesthetic block noted. At delivery, neonatal status was evaluated, and maternal and cord blood samples were obtained for local anesthetic assays and neonatal blood gases. The groups were similar with respect to maternal characteristics, onset of surgical anesthesia, time to delivery, and uterine incision-delivery interval. Maternal blood pressure decreased from control values in both groups (P less than 0.05), but there was no difference between the groups in either the incidence of hypotension or ephedrine requirements. Analysis of FHR tracings by a perinatologist blinded to the study group revealed no changes after anesthesia and no significant differences between the groups at any time in basal FHR, short- or long-term variability, or the incidence of accelerations or decelerations.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovine fetal cardiorespiratory response to nicardipine.

Nicardipine, a calcium antagonist associated with decreased uterine blood flow in near-term pregnant rabbits and fetal asphyxia after maternal administration in the rhesus monkey and sheep, was infused directly to the fetus in six chronically prepared pregnant ewes at 128 days' gestation. Changes in fetal mean arterial and diastolic blood pressure levels at 2 and 30 minutes after bolus injection of 50 micrograms were minimal; by 60 minutes these values had returned to preinfusion levels. No significant changes were observed after infusion of 100 micrograms of nicardipine. Fetal heart rate, fetal arterial blood gas values, and maternal cardiovascular variables did not change at either dose. Fetal plasma concentrations of nicardipine were 78 +/- 28 ng/ml and 114 +/- 48 ng/ml at 30 minutes after infusion of 50 micrograms and 100 micrograms, respectively, well within the range previously reported to be associated with fetal asphyxia. These data suggest that the previously reported fetal acidosis from maternal infusion of nicardipine may be primarily due to a decrease in maternal uterine blood flow rather than a direct fetal effect of the drug.

Cardiovascular and metabolic effects associated with nifedipine and ritodrine tocolysis.

Recent investigations have indicated that nifedipine, a calcium channel entry blocker, may be useful in the treatment of preterm labor. This prospective, randomized study compares cardiovascular and metabolic effects measured in association with sublingual and oral administration of nifedipine with those noted with the intravenous and oral administration of the beta-adrenergic agent ritodrine. Serial measurements of cardiovascular parameters, hematocrit, electrolytes, glucose, blood urea nitrogen, creatinine, calcium, and serum glutamic-oxaloacetic and glutamic-pyruvic transaminase were compared between groups. Sublingual and oral nifedipine caused minimal cardiovascular alterations. At doses sufficient to achieve tocolysis, ritodrine caused more pronounced cardiovascular changes than nifedipine. Both agents had a hemodilutional effect, but nifedipine was not associated with alterations in serum electrolytes or a dramatic hyperglycemia. On the basis of this study, it appears that the use of nifedipine for preterm labor management is associated with hemodilutional changes but not the adverse cardiovascular or metabolic effects often associated with ritodrine tocolysis.

Evaluation of a risk-scoring system for prediction of preterm labor.

A scoring system was used prospectively to screen 7329 patients for risk of preterm labor over a 6-year period. When 15.8% of patients (1156 of 7329) were scored as high risk, sensitivity was 42.4% (multiparas, 55.2%, nulliparas, 29.8%) and positive predictive value was 22.8%. The incidence of preterm labor increased with increasing risk score; gestational age at delivery was negatively correlated with risk score. Analysis of individual factors revealed that more than half were not of predictive value in the population under investigation. A simplification of the system, defining 12 of the factors as major (high risk) and six as minor (2 or more indicates high risk) yielded a high risk group of 14.1%, sensitivity of 41.0%, and positive predictive value of 24.6%. Thus, although risk scoring does predict a substantial proportion of patients with preterm labor, its sensitivity is less than ideal. No advantage was gained with a larger and more complex system. Planning for preterm birth prevention programs should include recognition of the limitations of risk scoring, consideration of simplified systems, and investigation of additional biochemical or biophysical screening methods.

Tocolytic and cardiovascular effects of the calcium antagonist diltiazem in the near-term pregnant rabbit.

Parturition was induced with a 1 U intravenous bolus dose of oxytocin in two groups of near-term pregnant rabbits chronically prepared with distal aortic catheters. One group (n = 7) received an intravenous infusion of diltiazem (270 micrograms/kg/min) and the other (n = 7) received saline solution. Parturition was markedly inhibited in the diltiazem-treated group, based on the time to delivery of the first and subsequent fetuses and the number of fetuses undelivered at the end of each study. A significant decline in maternal blood pressure was observed in the diltiazem-treated group, but no significant change in maternal heart rate occurred. These findings suggest that diltiazem may provide significant tocolysis without the reflex tachycardia that has been observed with other calcium antagonists. Further evaluation of the maternal and fetal cardiovascular effects of diltiazem as well as the establishment of lower effective tocolytic doses are warranted.

Biamnial elevated alpha-fetoprotein and positive acetylcholinesterase in twins, one with anencephaly.

Anencephaly in twin B was accompanied by elevated amniotic fluid alpha-fetoprotein (AFP) and a positive acetylcholinesterase (AChE) band on gel electrophoresis in both twin sacs, although twin A was normal. AChE results did not help distinguish the false positive AFP in this set of twins, implying that AChE may diffuse transamniotically as has been previously postulated for AFP. In light of the low concordance rate for neural tube defects in twins, patient counselling in this situation must include the information that AFP and AChE may be falsely elevated in normal twin when the other twin has a neural tube defect.

Evaluation of the weekly cervical examination in a preterm birth prevention program.

The efficacy of regular cervical examinations in detecting preterm labor, as well as possible risks, was studied for 133 preterm labor patients who had received regular cervical examinations as part of a preterm birth prevention program. When compared to all other patients experiencing preterm labor during the study period, the rates of preterm premature rupture of the membranes, chorioamnionitis, and postpartum endomyometritis were not increased. For 95 patients with preterm labor within 7 days of a routine cervical examination, labor onset was not temporally associated with the preceding examination. Preterm labor was diagnosed in 18 asymptomatic patients (18.2%) when the weekly examination revealed cervical change. Routine cervical exams, therefore, did not increase morbidity, and for some patients identified preterm labor before symptoms appeared.

Efficacy of Doppler echocardiography in the evaluation of aortic stenosis during pregnancy.

The recently developed technology of Doppler echocardiography was used to evaluate a pregnancy complicated by aortic stenosis. Given the lack of established norms for this test during pregnancy and the known cardiovascular changes during pregnancy, it is difficult to interpret this test. However, in the case presented, this test suggested the need for more conservative management, a plan that was justified postpartum.

Adjunctive magnesium sulfate infusion does not alter metabolic changes associated with ritodrine tocolysis.

Magnesium sulfate, an agent whose cellular actions might cause metabolic disturbances, has been used concomitantly with ritodrine hydrochloride for preterm labor tocolysis. Although the profound metabolic effects of beta-adrenergic agents have been well described, the possibility that adjunctive magnesium might cause further or unexpected alterations in maternal metabolic parameters has not been fully evaluated. To investigate this question, we prospectively randomized patients, in a blinded fashion, to receive ritodrine plus placebo or ritodrine plus adjunctive magnesium sulfate for preterm labor tocolysis. Serial measurements of potassium, glucose, blood urea nitrogen, and hematocrit were obtained and compared between tocolytic treatment groups. The metabolic changes found were similar in each group and appear to result predominantly from beta-adrenergic stimulation with no apparent perturbations caused by the direct cellular actions of magnesium sulfate. From the metabolic standpoint, it appears that the clinician may use adjunctive magnesium sulfate without fear of accentuating or obscuring the expected beta-adrenergic-induced alterations in the above-mentioned maternal metabolic parameters.