Maternal serum alpha-fetoprotein screening: report of a Canadian pilot project.

A pilot project of maternal serum alpha-fetoprotein (MSAFP) screening was carried out in Ontario from 1982 to 1985 to examine the feasibility and acceptability of screening a prenatal population for open fetal neural tube defects. A total of 8140 patients at low genetic risk were screened. Patient acceptance was excellent. Blood samples were taken at 16 to 18 weeks'' gestation. If the MSAFP level was elevated, the assay was repeated and an ultrasound examination performed. Amniocentesis was offered to 67 women with unexplained persistently elevated levels. The outcome of pregnancy was known in 7473 patients (91.8%). Seven of nine known open fetal neural tube defects were detected. All were confirmed, and no unaffected fetuses were aborted on the basis of the screening results. The rates of perinatal death (6.7%), intrauterine growth retardation (11.7%) and prematurity (23.3%) were significantly higher among the patients with unexplained elevated MSAFP levels than among those with normal levels (p less than 0.001). Of 20 patients with unexplained low levels, 10 subsequently had spontaneous abortions and 10 gave birth to term appropriate-for-gestational-age infants. Seven of nine patients who gave birth to infants with autosomal trisomy had MSAFP values below the median. The findings indicate that MSAFP screening is feasible, accurate and acceptable in a low-risk area.     

Maternal serum alpha-fetoprotein screening activities of state health agencies: a survey.

Maternal serum alpha-fetoprotein (MSAFP) screening has been demonstrated to be cost-effective on a population basis and is becoming standard practice. The American Society of Human Genetics has twice published policy statements to define the essential elements of a quality screening program. The present study reviewed the impact of these policy statements on state public-health agencies with respect to regulation or provision of MSAFP screening in their jurisdictions. With a few exceptions, states have not elected to play a major role in provision or regulation of this test. There is need to address issues of funding, standards, and data collection in a collaborative effort, if policy statements on genetic services are to be translated into effective state population screening.     

A maternal serum screen for trisomy 18: an extension of maternal serum screening for Down syndrome.

The feasibility of extending second-trimester maternal blood screening for Down syndrome so as to include screening for trisomy 18 was examined using stored maternal serum samples collected for neural tube-defect screening. There were 12 samples from trisomy 18 pregnancies and 390 controls. The median maternal serum concentration of alpha-fetoprotein, free alpha-subunit human chorionic gonadotrophin, free beta-subunit human chorionic gonadotrophin, intact human chorionic gonadotrophin, total estriol, unconjugated estriol, estradiol, human placental lactogen, and progesterone were lowered in those pregnancies affected by trisomy 18 when compared with unaffected pregnancies matched for racial origin, maternal age, gestational age, and sample-storage duration. At an estimated odds risk of 1:400, 83.3% of affected pregnancies were detected using an algorithm which combines the maternal age-related risk with the maternal serum concentrations of unconjugated estriol, free alpha-subunit human chorionic gonadotrophin, free beta-subunit human chorionic gonadotrophin, estradiol, and human placental lactogen. The associated false-positive rate was 2.6%. At high risk odds of 1:10, the detection rate was 58.3%, with an associated false-positive rate of 0.3%. beta-Subunit human chorionic gonadotrophin and unconjugated estriol were the most powerful discriminators. It is possible to incorporate into existing Down syndrome screening programs an algorithm for detecting trisomy 18 with high sensitivity and specificity.     

Measurement and use of total plasma homocysteine. American Society of Human Genetics/American College of Medical Genetics Test and Transfer Committee Working Group.

Hyperhomocysteinemia, which is a recognized independent risk factor for premature vascular occlusion, is defined as a fasting total plasma homocysteine (tHcy) level >15 microM. There may also be graded increased risks for persons with tHcy concentrations of 10-15 microM. The measurement of tHcy requires precise sample collection, immediate separation and freezing of plasma, and referral to a specialized laboratory. The etiologies of hyperhomocysteinemia are complex and involve both genetic and environmental factors. Because the inappropriate supplementation of involved cofactors can be harmful, it is important to identify the cause of hyperhomocysteinemia prior to treatment.     

Screening for fetal malformations using ultrasound and measurements of alpha-fetoprotein in maternal serum.

Fetal ultrasound combined with semiquantitative measurements of alpha-fetoprotein in maternal serum was used for early detection of neural tube defects and omphalocele in 10 147 pregnancies. The accurate assessment of gestational age, obtained by ultrasound, facilitated evaluation of alpha-fetoprotein concentrations in selecting cases for amniocentesis. The advantage of screening with two independent methods is suggested by the finding that eight out of 10 cases with malformations (spina bifida, encephalocele, anencephalus, omphalocele) were detected when both methods were used. Screening by routine ultrasound alone detected only four malformations and by measurement of alpha-fetoprotein alone only seven. The results suggest that, in a low risk population, ultrasound should be combined with the measurement of alpha-fetoprotein in screening for neural tube defects. Measurement of alpha-fetoprotein is indispensable in detection of the small neural tube defects, where the fetus would survive with severe sequelae. The semi-quantitative analysis of alpha-fetoprotein that may be used in combination with ultrasound examination is of negligible cost.