Decreased maternal serum hCG levels with increasing gravidity and parity.

OBJECTIVE: To investigate the preliminary observation that primigravid women have higher hCG multiples of the median (MoM) than multigravid women. METHODS: An analysis of the effect of gravidity and parity on maternal serum alpha-fetoprotein (MSAFP) and hCG was performed using data from 20,009 consecutive singleton pregnancies of 15-20 weeks' gestation in a maternal serum screening program. RESULTS: The human chorionic gonadotropin MoM for primigravid women was 0.1 MoM higher than for multigravid women. As parity or gravidity increased, maternal serum hCG decreased. The median hCG MoM for nulliparous women was 1.05, compared with 0.94 MoM for para 3 women. The decrease in hCG was similar at each gestational week from 15-20. In contrast, MSAFP and MSAFP MoM were unaffected by parity. Maternal age and race were potential contributing factors to the effect of parity. However, the decrease in hCG MoM with parity was observed within each 5-year increment of maternal age. Similarly, both black and non-black populations displayed decreases in hCG with parity, although black women had a consistently higher MoM in all matched sets. The decrease in hCG MoM with parity was also observed in 50 Down syndrome cases. Correcting patient data for parity resulted in the hCG MoM changing only 2.7% on average. The detection rate for the 50 Down syndrome cases would not have changed. CONCLUSION: The decrease in maternal serum hCG with increasing parity demonstrates that pregnancy history influences the level of maternal serum hCG. Further studies are needed to define the contributing factors, but the impact of parity on Down syndrome screening appears to be small.

Effectiveness of combining maternal serum alpha-fetoprotein and hCG in a second-trimester screening program for Down syndrome.

OBJECTIVE: To evaluate the efficacy of combining hCG and alpha-fetoprotein (AFP) with maternal age in a two-analyte maternal serum screening program for Down syndrome. METHODS: A prospective study involved the screening of 12,170 maternal sera from patients at 14-25 weeks of gestation. The risk for Down syndrome at term was calculated from maternal serum hCG and AFP, and maternal age. For women 36 years of age and younger, a risk of 1:307 or greater was considered screen-positive. For women over 36, a risk greater than that a priori was considered screen-positive. False-positive rates and detection rates were compared with those resulting from a screening protocol using only AFP and age. RESULTS: Seven hundred eighty-two sera were initially screen-positive (6.4%). Subsequent sonography decreased this total to 687 (5.6%), and 467 (3.8%) of these patients accepted amniocentesis. Ten cases of Down syndrome and seven other chromosomal abnormalities were detected. Follow-up investigations revealed eight additional Down syndrome cases that were missed by screening. The identification of 18 Down syndrome cases in 12,170 pregnancies corresponds closely with the prediction of 14.1 Down syndrome births (18.2 second-trimester fetuses) in this population calculated from age-dependent risks. The detection rate for Down syndrome was 56% (ten of 18 expected cases). Only five of 18 (28%) would have been detected by AFP and age alone. CONCLUSION: These results support the mathematical model that hCG is the major contributor to the increased sensitivity of multi-analyte screening and demonstrate that screening programs can attain substantial improvement in detection of second-trimester Down syndrome by adding hCG to AFP and age.

Combined serum amylase and lipase determinations for diagnosis of suspected acute pancreatitis.

Serum amylase and lipase measurements are often used to diagnose acute pancreatitis. This study addresses the question of whether it is advantageous to order serum amylase and lipase tests simultaneously. We evaluated performance of the two tests separately and in combination through a retrospective study of patients for whom both amylase and lipase determinations were ordered. Initial analysis of test performance was conducted with a uniformly applied criterion based on determination of optimal sensitivity-specificity pairs. Individual tests and combinations of tests, including the "AND" and "OR" rules and discriminant functions, were examined. Only the discriminant approach demonstrated better performance than the lipase test alone. This finding was subsequently confirmed by logistic regression analysis. We conclude that ordering both tests simultaneously can be advantageous in diagnosing acute pancreatitis when a bivariate approach is used; however, this must be weighed against the difficulties associated with clinical implementation of such approaches.

Relevance of common tests of cerebrospinal fluid in screening for bacterial meningitis.

This study tests the hypothesis that if cerebrospinal fluid (CSF) has a nucleated blood cell count (NucBC) of less than 6/mm3, CSF tests other than bacterial culture need not be performed to exclude the diagnosis of bacterial meningitis in patients not receiving antimicrobial agents. The results of tests performed on the first specimen of CSF obtained for a given hospital visit from children younger than 3 years of age, exclusive of newborn infants admitted to the hospital on their date of birth, were analyzed. Of 3356 CSF specimens evaluated, 122 were from patients with bacterial meningitis; 460 specimens were analyzed separately because the erythrocyte count was greater than 1000/mm3. A negative CSF screening test result was defined as a CSF NucBC less than 6/mm3. In facilitating the diagnosis of bacterial meningitis, this screening test had a sensitivity of 98.4%, a specificity of 75.2%, and a negative predictive value of 99.9%. The other CSF tests varied widely in screening effectiveness: a Gram-stained smear had a sensitivity of 53% and a specificity of 97%. Receiver operating characteristic curve analysis was used to assess the screening relevance of CSF tests. The CSF NucBC and CSF segmented NucBC performed indistinguishably and superiorly compared with the CSF protein or glucose concentration and the ratio of CSF glucose to serum glucose concentration. Logistic regression analysis showed that the NucBC alone is superior to any combination of the other CSF tests. In a prospective study of 215 children younger than 3 years of age undergoing a lumbar puncture in our emergency department, 85% had empiric criteria identifying them as appropriate for an abbreviated CSF evaluation. The CSF NucBC was less than 6/mm3 in 70% of the 181 patients who would have been eligible for an abbreviated CSF evaluation. These data suggest that a strategy for the sequential testing of CSF could be adopted that would exclude unnecessary determinations and thereby save time, effort, and health care dollars.

Simultaneous determination of cerebrospinal fluid oligoclonal bands and the "gamma-protein index" by agarose electrophoresis and densitometry.

Oligoclonal bands were identified in electropherograms of cerebrospinal fluid, and the "gamma-protein index" was concurrently calculated from the same strip. For the index, an upper limit of normal of 0.66 was established. We compared results with the clinical diagnosis in 69 patients with multiple sclerosis and 48 control patients with other diseases. Sensitivity, specificity, and positive predictive values of 73%, 96%, and 96%, respectively, were obtained from the index. An abnormal index and the presence of oligoclonal bands combined increased the positive predictive value to 100%. This approach may allow adequate qualitative and quantitative assessment of gamma-globulin abnormalities in cerebrospinal fluid after a single laboratory procedure.

Glutamate dehydrogenase in Reye's syndrome. Evidence for the presence of an altered enzyme in serum with increased susceptibility to inhibition by GTP.

The glutamate dehydrogenase activity found in the serum of patients with Reye's syndrome is shown to be inhibited about 1000-fold more potently by GTP than is the normal human enzyme. 1 mM ADP, which with the normal enzyme effectively reverses GTP inhibition, has no effect in the GTP inhibition of the Reye's syndrome serum activity.

Masking by enzyme inhibitor of raised serum glutamate dehydrogenase activity in Reye's syndrome.

Serum glutamate dehydrogenase (GDH) activity was greatly raised (up to 830 times the upper limit of normal) in 16 patients with Reye's syndrome. The serum activity was masked by an inhibitor, and the rises were observed only after dialysis or sample dilution. Serum GDH values from 38 paediatric patients, including 10 with hyperammonaemia due to other causes, showed no such rise after dialysis. Only 1 of 13 adult patients with liver disease had high GDH activity, but this level was not increased after dialysis. Serum ornithine carbamyl transferase activity was also raised in patients with Reye's syndrome, but levels were not increased after dialysis. The ratio of dialysed/undialysed GDH activity clearly distinguished all Reye's patients from controls. The inhibition of a mitochondrial enzyme which regulates ammonia metabolism may contribute to the hyperammonaemia of Reye's syndrome. Serum GDH levels before and after dialysis would seem to be a useful diagnostic aid in Reye's disease.

Do preoperative laboratory tests predict blood transfusion needs in cardiac operations?

We retrospectively compared preoperative prothrombin (PT), partial thromboplastin (PTT), dilute whole blood clot lysis and bleeding times, fibrinogen level, and platelet count with subsequent blood component administration in 92 patients who had undergone cardiac operations with cardiopulmonary bypass (CPB). Abnormal results for one or more tests were found in 34% of 71 adults and 81% of 21 children and teenagers. The patients with abnormal test(s) received no more whole blood and packed red cell units, platelets, or plasma than those with normal tests in either age group. No individual or multiple test abnormalities predicted excess blood component transfusion, even when low-grade abnormalities were excluded. The high rate of abnormal tests in patients less than 20 years of age was not due to polycythemia and may indicate a need for age-specific reference ranges. Baseline PT, PTT, and platelet count may aid in the evaluation of the potential for subsequent development of coagulopathy, but we conclude that further preoperative testing may be reserved for infants, polycythemic individuals, or others in whom history or drug use suggests potential bleeding problems.

Spurious elevation of the electronically determined mean corpuscular volume and hematocrit caused by hyperglycemia.

Following normalization of blood glucose levels, a marked change in the MCV and in the calculated hematocrit was observed in five patients with transient severe hyperglycemia. The addition of varied concentrations of glucose to blood samples from healthy volunteers and from patients with microcytic, macrocytic, and normocytic anemia produced a similar and proportionate increase in the MCV. Increases in urea concentration to clinically relevant levels had no effect. The phenomenon appears to result from the osmotic swelling and subsequent shrinking of hyperglycemia erythrocytes when they are mixed with the diluent used for measurement of hematologic parameters. The magnitude of this spurious macrocytosis is less pronounced with the Coulter S than with the Coulter S-Plus. This difference can be explained by the differences in incubation prior to measurement of these instruments. A method for eliminating this spurious finding in blood samples with high levels of glucose is recommended.

Isoelectric focusing of hemoglobins on thin-layer agarose.

Isoelectric focusing on thin layers of agarose was used to separate several human hemoglobin variants in narrow pH range (pH 6-9). Problems with gel flooding and distortions due to electroendosmotic flow were solved by altering the casting and processing of the gel, by modifying the focusing apparatus, and by utilizing commercial agarose that had been chemically modified to reduce electroendomosis. Hemoglobins C, O-ARAB, A2, and E were distinguished from one another, as were hemoglobins S, D-LOS ANGELES, G-PHILADELPHIA, F. A, I, and J. The technic is rapid, simple, and relatively inexpensive. The agarose is nontoxic, has excellent gelling properties, and possesses large pores, yet gives resolution equivalent or superior to that obtained on thin layers of polyacrylamide gel, making it preferable to polyacrylamide for thin-layer isoelectric focusing.

alpha-Fetoprotein in the routine clinical laboratory: evaluation of a simple radioimmunoassay and review of current concepts in its clinical application.

We have assessed the clinical utility of a radioimmunoassay for alpha-fetoprotein (AFP). The method, which relies on ammonium sulfate precipitation for the separation of "bound" and "free" radiolabeled antigen, can be completed in one working day. The assay is specific for AFP, has a sensitivity of < 10 ng/ml, and has intra- and inter-assay precision of 5--8% and 9--11%, respectively. We have conducted a three-year study of 472 pregnancies in which physicians wished to detect neural tube defects, and of 400 non-pregnant patients to assess the value of serum AFP as a marker for certain benign and malignant diseases. Six of 6 fetal open neural-tube defects (NTD's) and 3 of 3 intrauterine fetal deaths were correctly identified by their association with marked AFP elevations in both maternal serum and amniotic fluid. Thirty non-pregnant patients were found to have AFP elevations greater than 20 ng/ml. Malignancies associated with these elevations were hepatoma, germ cell tumors, Wilms' tumor, and carcinoma of unknown origin. Carcinoma metastatic to the liver was not associated with AFP elevations. In AFP-associated tumors we found serial measurements of serum AFP to be of value in assessing therapeutic response. Benign diseases associated with AFP elevations included neonatal hepatitis, viral hepatitis, fulminant toxic hepatitis, and cryptogenic cirrhosis.

Fetal-maternal bleeding associated with genetic amniocentesis.

Maternal serum alpha-fetoprotein (AFP) elevation following midtrimester genetic amniocentesis (post-AFP) was studied as an indicator of fetal-to-maternal bleeding (FMB). A post-AFP elevation was observed in 28 of 333 (8.4%) consecutive patients who before the procedure had preliminary placental localization by ultrasound and a normal serum AFP concentration (pre-AFP) for the gestational age. The absolute elevations of post-AFP and serial AFPs and the correlation with placental localization all suggest that this is related to FMB. The frequency of spontaneous abortion in patients with an elevation of post-AFP (4 of 28 cases, 14.29%) as opposed to the frequency of those patients who did not demonstrate this phenomenon (3 of 305, 0.98%) was significantly different. The higher frequency of anterior placental implantations in the former group suggests that preliminary placental localization by ultrasound may be important when counseling the patient concerning the risk of amniocentesis. The implications of these findings regarding Rh sensitization and the need for Rh immunoglobulin prophylaxis following this procedure are discussed.