Elevated maternal serum alpha-fetoprotein with low unconjugated estriol and the risk for lethal perinatal outcome.

OBJECTIVE: To determine whether a combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low unconjugated estriol (E3) concentration identifies pregnancies at particularly high risk for fetal abnormality or poor outcome. METHODS: Pregnancy outcomes were reviewed for women with elevated MSAFP (> or =2.0 MoM) from our database of 50,315 women who had received triple marker testing from 1993-1998. Outcomes for those with low E3 (< or =0.7 MoM) were compared with those with normal E3 (>0.7 MoM). The incidences of fetal death, neural tube defects, chromosome abnormalities, congenital abnormalities, preterm birth, small-for-gestational age (SGA), twins, and inaccurate dates were compared in the two groups using Fisher's exact test with P < 0.05 considered significant. RESULTS: Of the 50,315 women screened, 1,435 (2.85%) had an elevated MSAFP. Pregnancy outcomes were obtained in 94% of those with elevated MSAFP and 70% of all patients screened. Neural tube defects were present in 57 fetuses/infants (21 anencephalic, 29 spina bifida, 7 encephalocele) of which 46 (81%) had an elevated MSAFP. Of the 1,435 women with an elevated MSAFP, 199 (14%) had a low E3. Compared to those women with elevated MSAFP but normal E3, women with elevated MSAFP and low E3 were at significantly increased risk for fetal death (20.6% vs. 2.8%, relative risk (RR) 8.9), anencephaly (9.0% vs. 0.1%, RR 122.8) and chromosome abnormality (2.5% vs. 0.6%, RR 4.0). CONCLUSIONS: Pregnancies complicated by elevated second trimester MSAFP and low E3 are at a particularly high risk (32%) for lethal perinatal outcomes. Twins, while a common cause of elevated MSAFP, are rarely found when an elevated MSAFP is associated with low E3.

Look on the bright side: a case study of uveitis.

This article explores the contemporary approach to the care of patients with uveitis, an inflammation of the uvea or middle layer of the eye, including the etiology, symptoms, diagnosis, types, and contemporary treatment of this serious ophthalmic condition. Uveitis represents the third-leading cause of blindness in developed countries. Vision loss with this disease occurs usually as a result of very slow damage to the macula, which is the consequence of low-grade chronic inflammation. A case study involving a young man with uveitis is used to demonstrate the importance of treating active inflammation aggressively rather than waiting for a particular level of degradation. The role of the professional nurse is highlighted because the support, care, and education of this patient appear to be major components to his well being.

Trisomy 16 mosaicism in amniotic fluid cell cultures.

Trisomy 16 mosaicism was found in amniotic fluid cells in a patient undergoing amniocentesis because of elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) (2.80 MOM), a markedly elevated human chorionic gonadotropin level (hCG) (12.02 MOM), and a Down syndrome risk of 1:55. Ultrasound evaluation of the fetus indicated the presence of an atrial septal defect and clinodactyly. Cytogenetic analyses of various fetal tissues using fluorescence in situ hybridization (FISH) failed to detect substantial numbers of trisomy 16 cells; however, trisomy 16 mosaicism was identified in placental tissue. Molecular genetic analysis at five different loci [four analysed by polymerase chain reaction (PCR) and one by Southern blot analysis] failed to show any evidence for uniparental disomy. Although trisomy 16 cells could not be clearly demonstrated in the fetus, the presence of a clinically significant proportion of aneuploid cells early in development could not be excluded and it therefore cannot be assumed that a 'confined placental mosaicism' existed. The markedly elevated hCG and elevated MSAFP levels are consistent with abnormal placental function in trisomy 16 mosaicism. Serial ultrasound evaluation (to detect any late-onset growth retardation) and fetal echocardiography may be indicated for patients with extraordinarily high levels of hCG, especially if MSAFP is also elevated.

Maternal serum screening for birth defects: results of a Connecticut regional program.

Second trimester maternal serum screening provides a method to identify pregnancies at high risk for fetal Down's syndrome, trisomy 18, open neural tube defects, and a variety of other chromosomal and nonchromosomal fetal anomalies. Results are presented for a regional program to identify high-risk pregnancies using alpha feto-protein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) analyses (triple marker testing). A total of 27,140 women received screening. Using a midtrimester Down's syndrome risk of 1:270 to define the high-risk group, 5.26% of women of all ages were screen-positive for Down's syndrome resulting in the eventual detection of approximately 72% of the affected fetuses. The detection rate for patients under 35 at estimated date of delivery was 61% and for women 35, or older, the detection rate was 100%. A separate protocol to screen for trisomy 18 identified 0.2% of pregnancies, with 38% of the trisomy 18 cases present in this group. Over 3% of women screen-positive for Down's syndrome or trisomy 18 had a serious fetal chromosome anomaly. In addition, 2.89% of women had an elevated AFP (greater or equal to 2.0 multiples of median). This component of the screening resulted in the identification of 86% of the neural tube defects, 75% of the ventral wall defects, and also some of the other various fetal anomalies present in the screened population. Since both laboratory and clinical data are combined to generate patient-specific risks, there is a need for quality control elements that go beyond that normally required for a clinical laboratory alone. We stress the need for comprehensive follow-up programs to evaluate screening programs and maintain high quality.

Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2 alpha or intravaginal prostaglandin E2 suppositories: a randomized trial.

OBJECTIVE: To compare intramuscular (IM) prostaglandin 15 methyl-F2 alpha (15M-PGF2 alpha) with prostaglandin E2 (PGE2) vaginal suppositories for second-trimester abortion in terms of efficacy and side effects. METHODS: Fifty-one women were randomized to receive either 15M-PGF2 alpha IM injections or PGE2 intravaginal suppositories for second-trimester abortion. Efficacy and side effects of the two agents were analyzed by two-tailed t tests, chi 2 analysis with Fisher exact test, and survival analysis. RESULTS: The mean times to rupture of membranes, delivery of fetus, and delivery of placenta were significantly less for women receiving PGE2 vaginal suppositories. The cumulative abortion rate after 24 hours for the PGE2 group was 96%, compared with 69% for the 15M-PGF2 alpha group. Although there were few differences in side effects, the 15M-PGF2 alpha group had significantly fewer headaches, fevers, and chills. CONCLUSION: Intravaginal PGE2 is superior to IM 15M-PGF2 alpha for second-trimester abortion.

Efficacy of the biparietal diameter/femur length ratio to detect Down syndrome in patients with an abnormal biochemical screen.

Abnormal fetal biometry is considered a marker for fetal trisomy. We prospectively evaluated the biparietal diameter/femur length ratio to identify Down syndrome fetuses. This ratio was calculated when women (< 35 years old) underwent an amniocentesis for an abnormal biochemical screen for Down syndrome. Using reported ratio cut-offs (> 1.5 SD above the mean), the ratio had a sensitivity of 50% (3/6), specificity of 92% (244/264), positive predictive value of 13% (3/23), negative predictive value of 99% (244/247), and a relative risk of 10.8. Using our own population ratio, a cut-off > 1.5 SD had a sensitivity of 50% (3/6), specificity of 94% (249/252), positive predictive value of 17% (3/18), negative predictive value of 99% (249/252) and a relative risk of 13.9. A lower cut-off decreased the efficacy to detect Down syndrome. A ratio > 1.5 SD above the mean is a useful adjunct to identify Down syndrome in pregnancies at risk by an abnormal biochemical screen.

Ear length in second-trimester aneuploid fetuses.

OBJECTIVE: To test the hypothesis that small ears have diagnostic value in detecting second-trimester aneuploid fetuses by ultrasound. METHODS: We prospectively studied 452 patients with singleton pregnancies undergoing ultrasound examination for genetic amniocentesis at 14-25 weeks and an additional 30 singleton pregnancies at 20-25 weeks with a negative anomaly screen. Standard fetal biometry measurements were obtained, including ear length (from helix to end of lobe). RESULTS: Of these patients, 424 (88%) had ear measurements obtained, and a nomogram for ear length by gestational age was compiled. The relationship between ear length and gestational age was linear across the second trimester (r = 0.84, P < .001). Fourteen fetuses had aneuploidy by amniocentesis, of whom ten had ear lengths at or below the tenth percentile. The sensitivity was 71% and the specificity 92% (377 of 410). Positive and negative predictive values were 23% (ten of 43) and 99% (377 of 381), respectively. CONCLUSION: Fetal ear length may be useful in identifying aneuploid fetuses sonographically during the second trimester.

Calculated risk of chromosomal abnormalities in twin gestations.

Genetic counseling concerning the risks of chromosomal abnormalities in twin gestations can be difficult; the risk of amniocentesis is weighed against that of chromosomal abnormalities in either one or both of the twins. Because most twins are dizygotic (each with a risk a priori of aneuploidy), the chance that one of the fetuses is affected is greater than would be expected for a singleton. Only three possibilities would result in either one or both twin's being affected: 1) dizygotic twins with one fetus affected, 2) dizygotic twins with both fetuses affected, and 3) monozygotic twins with both fetuses affected. Using existing tables of estimated risks of chromosomal abnormalities in singleton gestations and mathematically derived formulas, we created tables defining the age-related risks of chromosomal abnormalities in twin gestations. According to these tables, a patient at 33 years of age with a twin gestation has a risk of Down syndrome in at least one of her twins equivalent to that of a 35-year-old with a singleton. Prenatal genetic testing should be considered for women with twins at a younger age than the traditional 35.