Alexander Baumgarten

Screening for Fetal Down's Syndrome in Pregnancy by Measuring Maternal Serum Alpha-Fetoprotein Levels

Although the risk of Downs syndrome increases with maternal age, women under 35 bear about 80 percent of the infants born with this condition. We prospectively investigated the utility of measuring maternal serum alpha-fetoprotein during the second trimester in women under 35 in order to identify pregnancies in which the fetus was affected with Downs syndrome. Over a two-year period, 34,354 women in this age group were screened. Amniocentesis was offered when the risk of Downs syndrome, calculated as a function of maternal age and maternal serum alpha-fetoprotein concentration adjusted for maternal weight and race, was 1:270 or higher, the risk for a 35-year-old woman. This threshold was exceeded in 1451 women in whom gestational age was confirmed by ultrasound; 9 women in this group had a fetus with the syndrome. In three women whose fetuses had trisomy 18 and one whose fetus had trisomy 13, the calculated risk of Downs syndrome was 1:270 or higher. Thus, among women in whom the risk exceeded our cutoff point, 1 in 161 were found to have a pregnancy in which the fetus was affected with Downs syndrome; the figure was 1 in 112 for all autosomal trisomies. Eighteen pregnancies involving Downs syndrome, three involving trisomy 18, and two involving trisomy 13 were not associated with a calculated risk above the cutoff point. The available data indicate that in our population, using a cutoff for risk at which 5 percent of women under 35 are offered amniocentesis, we will detect one quarter to one third of pregnancies in which the fetus has Downs syndrome.

New Down syndrome screening algorithm: ultrasonographic biometry and multiple serum markers combined with maternal age.

OBJECTIVE We compared the Down syndrome screening efficiency of a new algorithm that combines humerus length measurement and serum analytes versus that of the traditional triple-analyte serum screen. STUDY DESIGN Humerus length measurements were obtained prospectively in 1743 midtrimester (14 to 24 weeks) singleton fetuses before genetic amniocentesis. All patients had triple-marker serum screening before amniocentesis. Data on humerus length were expressed as multiples of the median, and were normalized by log transformation. Backward multiple stepwise logistic regression analysis was performed to determine which combination of biometry and serum markers best predicted fetal Down syndrome. The screening efficiency of the traditional triple-analyte algorithm was compared with that of a new multivariate gaussian algorithm that combined biometry and serum markers. RESULTS There were 31 (1.8%) fetuses with Down syndrome in the study population. In the regression analysis humerus length, human chorionic gonadotropin, alpha-fetoprotein, and maternal age were significant predictors of Down syndrome, but unconjugated estriol was not. The combined algorithm (humerus length, human chorionic gonadotropin, and alpha-fetoprotein and age) was superior to the traditional triple screen for Down syndrome detection. The sensitivities at fixed false-positive rates were consistently higher in the combination than in the triple-screen protocol. For example, at a 10% false-positive rate the sensitivities were 65.0% and 52.3%, respectively. Similarly, at a 15% false-positive rate the sensitivities were 73.5% and 55.0%, respectively. CONCLUSION A new screening algorithm combining humerus length and serum analytes was superior to the traditional triple screen. Although we used a high-risk population in this study, it is expected that the observed superiority of the combination screen would persist in a population of younger women. The development of a combined biometric and serum analyte screening algorithm for estimating individual odds could represent an advance in prenatal Down syndrome screening.

Rise in maternal serum α-fetoprotein concentration after chorionic villus sampling and the possibility of isoimmunization

Maternal serum alpha-fetoprotein concentrations were determined by radioimmunoassay in 72 patients immediately before and after chorionic villus sampling for prenatal diagnosis. Fifty percent showed a rise of greater than or equal to 5 ng/ml. Assuming such rises represent fetal blood crossing the intervillous space, in 14% of the cases greater than or equal to 60 microliters of fetal blood was transferred at the time of chorionic villus sampling. A positive correlation was found between the magnitude of rise in maternal serum alpha-fetoprotein levels and the amount of villi removed (r = 0.39, p less than 0.001). When cases were examined by number of passes, a greater rise in maternal serum alpha-fetoprotein levels was noted with multiple passes than with single passes for a given sample size. The transfer of greater than or equal to 60 microliters of fetal blood suggests that maternal sensitization to fetal antigens may occur after chorionic villus sampling. During biopsy, as small a sample of villi as necessary for diagnosis should be taken with as few catheter passes as possible.

Combined ultrasound biometry, serum markers and age for Down syndrome risk estimation

Objective To compare Down syndrome screening efficiency of the standard serum triple analyte screen to that of a four‐component screen consisting of ultrasound biometry and serum markers in the second trimester.

Immunoregulatory abnormalities in children withthrombocytopenic purpura

Twenty-eight children with idiopathic thrombocytopenia and 51 members of their immediate families were studied for immunologic function and expression of autoimmune phenomena and disease. Among patients with active ITP, 64% had defective immunoregulatory lymphocytes. The majority of patients (23/28) and family members had one or more immunologic abnormalities, including autoantibodies, other autoimmune disorders, and abnormalities in complement, immunoglobulins, or regulatory T lymphocytes. These data suggest that a genetic predisposition to autoimmunity is present in the majority of children with ITP.

Prospective study of an inverse relationship between maternal glycosylated hemoglobin and serum α-fetoprotein concentrations in pregnant women with diabetes

A hypothesized inverse relationship between the concentration of glycosylated hemoglobin and serum alpha-fetoprotein was observed in a prospective study of 39 pregnant women with insulin-dependent diabetes as well as seven pregnant women with diabetes who did not require insulin (r = -0.434, p less than 0.002). No similar correlation was found among a selected population of healthy pregnant women (r = -0.129). Because the level of glycosylated hemoglobin in pregnancy correlates with poor outcome, including the occurrence of fetal anomaly, it may be important to quantify glycosylated hemoglobin in pregnancies with low alpha-fetoprotein levels. These results also suggest that the maternal concentration of glycosylated hemoglobin can be used to adjust serum alpha-fetoprotein values before their interpretation in the screening of pregnant women with diabetes.

Amniotic fluid α-fetoprotein concentrations in twin gestations: Dependence on placental membrane anatomy

Placental membrane anatomy was evaluated after delivery in 65 twin pregnancies undergoing genetic amniocentesis with amniotic fluid alpha-fetoprotein and acetylcholinesterase determinations when indicated. Each twin member in the 57 uncomplicated twin pregnancies was found to have an amniotic fluid alpha-fetoprotein concentration similar to that of singleton pregnancies of an equivalent gestational age. Eight twin pregnancies were found to be discordant for fetal anomalies associated with an elevated amniotic fluid alpha-fetoprotein and acetylcholinesterase level. The amniotic fluid alpha-fetoprotein concentration in the unaffected fetus in these eight cases was found to be dependent on placental membrane structure. Of the five discordant twin pregnancies with diamnionic-dichorionic placentas, all unaffected twins demonstrated an amniotic fluid alpha-fetoprotein concentration within the normal range for gestational age with a normal acetylcholinesterase level. In three twin pairs with diamnionic-monochorionic placentas, the unaffected twin member had significantly elevated amniotic fluid alpha-fetoprotein and acetylcholinesterase levels, which suggested diffusion of alpha-fetoprotein and acetylcholinesterase through the amnion-amnion interface.

A reassessment of maternal serum alpha-fetoprotein in diabetic pregnancy

We assessed maternal serum alpha-fetoprotein (AFP) concentrations in 227 diabetic women who belonged to different groups of Whites classification but found no difference either between the insulin-dependent and the normative population or between the former and diabetics who were not insulin-dependent. By contrast, we found in maternal blood a marked, statistically significant inverse correlation between maternal serum AFP and the concentration of glycosylated hemoglobin in maternal blood assayed within 6 weeks of each other in mid-gestation (r = -0.4, p less than 0.05), but not when glycosylated hemoglobin was determined in the first two months of pregnancy (r = 0.05). These data indicate that the decrease in maternal serum AFP found in pregnant diabetic women is related to the efficacy of diabetic control but not to the diabetic status. A correction in maternal serum AFP should therefore be applied only to values obtained for women with poor glycemic control. Decreased maternal serum AFP in poorly controlled diabetics may indicate reduced synthesis of other fetal proteins which, in turn, may correlate with fetal growth retardation and the occurrence of malformation.

A lack of justification for routine screening assays for syphilis in general hospital psychiatric patients

Abstract Of 136,035 Yale-New Haven Hospital patients who had screening tests for syphilis, 1.2% were VDRL (Venereal Disease Research Laboratory) positive, and 0.6% were FTA-Abs (Fluorescent Treponemal Antibody Absorption) positive. Of this total sample, 2037 were psychiatric inpatients, 15 of whom were VDRL positive (0.7%), and only 4 (0.2%) were FTA-Abs positive. The authors discuss the merits of routine screening based on this and other surveys. The results of screening the psychiatric subsample were of particular interest since these patients might be at risk for misdiagnosis and brain dysfunction. Of this psychiatric inpatient cohort: (1) the number of syphilitics identified was 3.8-fold lower than that in the total sample, (2) strong consideration could be given to screening only those DSM-III ( Diagnostic and Statistical Manual of Mental Disorders [ed 3] ) diagnostic subgroups at risk, and (3) these were major affective disorders or delusional dementia. Further studies of other samples, psychiatric and nonpsychiatric, to define subgroups at risk are suggested.

E rosette formation in the presence of α-fetoprotein and ferritin

Abstract Formation of E rosettes has been reported to be inhibited by amniotic fluid and two carcinofetal proteins, α-fetoprotein (AFP) and α-2H, have been associated with the inhibition. α-2H has been reported to be immunologically identical with ferritin. This study has sought to evaluate the inhibition using amniotic fluid containing 5.8–150 μg of AFP per ml, two hepatoma sera containing 6.4 and 11 μg of AFP per ml, and solutions of ferritin containing 0.1–2.0 mg of protein per ml. Lymphocytes were obtained from 10 donors. Control lymphocyte preparations exhibited 74% (range 68–81%) E rosettes, lymphocytes incubated with amniotic fluid exhibited 73% (range 69–81%) rosettes, and those treated with ferritin 72% (range 68–79%) rosettes. It is concluded that neither AFP nor ferritin inhibits lymphocytes from forming E rosettes with sheep red blood cells.