Maternal Serum Alpha-fetoprotein Measurements Research Articles

Prenatal screening for neural tube defects: from maternal serum alpha-fetoprotein to ultrasonography.

The two main screening tests during pregnancy are those for chromosomal abnormalities and neural tube defects (NTDs). In particular, for NTDs, measurement of maternal serum alpha-fetoprotein (MSAFP) levels early in the second trimester (15-18 weeks of gestation) has been considered the gold standard screening test for the past 4 decades. However, with remarkable technological advancements and the widespread use of ultrasound during those periods, mid-trimester ultrasonography has gradually replaced the role of measuring MSAFP levels as a screening method for NTDs. This change was initiated more about 10 years ago in some countries, which have issued national guidelines to use mid-trimester ultrasonography instead of measuring MSAFP levels as a prenatal screening method for NTDs. However, no significant changes have occurred in Korea, where second-trimester ultrasonography is routinely performed with high-quality equipment. We aimed to provide information regarding the importance of changing the screening method for NTDs from MSAFP measurement to ultrasonography, and to detail methods of implementing mid-trimester ultrasonography for screening purposes. We also share our experience of operating a prenatal diagnostic program for NTDs without using MSAFP for more than 15 years.

Perinatal management of spina bifida

The management of patients with myelomeningocele is largely dependent on the timing of the diagnosis, i.e. ante- or postnatally. Antenatal diagnosis can be made using a combination of maternal serum alpha-fetoprotein measurement, fetal ultrasonography and, where necessary, amniocentesis.

First-Trimester Screening for Neural Tube Defects Using Alpha-Fetoprotein

Objective: To assess the potential value of maternal serum alpha-fetoprotein (AFP) at 11–13 weeks’ gestation in early screening for fetal neural tube defects (NTDs). Methods: Maternal serum AFP at 11–13 weeks’ gestation was measured in 32 cases of fetal NTDs, including 18 cases of acrania and 14 cases of spina bifida, and 1,500 unaffected controls. The measured serum AFP was converted into multiple of the expected median (MoM) after adjustment for gestational age and maternal characteristics and Mann-Whitney test was used to determine the significance of difference in the mean MoM of serum AFP in the NTD group to that in the controls. Results: The mean AFP MoM in the NTD group (1.76, 95% CI 1.39–2.23) was significantly higher than in the controls (p < 0.0001). The mean AFP MoM was not significantly different between the cases of acrania and cases of spina bifida (1.78 vs. 1.75; p = 0.722). The detection rates of NTD in screening by serum AFP were 50.0% (95% CI 31.9–68.1) and 37.5% (95% CI 21.1–56.3) at fixed false-positive rates of 10 and 5%, respectively. Conclusion: Measurement ofmaternal serum AFP at 11–13 weeks’ gestation may be useful in screening for fetal NTDs.

Identification of Second Trimester Screen Positive Pregnancies at Increased Risk for Congenital Heart Defects

Previous studies have shown that prenatal detection of a congenital heart defect (CHD) is associated with decreased morbidity and mortality. The investigators hypothesized that identification of second trimester biomarkers for CHD in maternal serum would identify patients who would benefit from fetal echocardiography and improve detection and outcomes of CHD―especially in pregnancies without other identified risk factors. This study investigated whether second trimester biomarkers considered in combination with ultrasound data could be used to identify screen positive pregnancies at increased risk of a CHD. The effect of using different biomarker cut points on observed CHD-biomarker relationships and on performance of predictive models was also assessed. The study population included 19,402 singleton pregnancies without chromosomal defects, which were screen positive for Down syndrome, trisomy-18 (T-18), a neural tube defect or other birth defects based on measurement of maternal serum alpha-fetoprotein, human chorionic gonadotropin (hCG), and unconjugated estriol. The associations between biomarkers and CHD were compared in cases and a control population using logistic regression models. The nuchal fold (NF) was measured by ultrasound in the second trimester. In models that considered screen positive grouping, CHD cases were more likely than controls to have a screen positive result for T-18 (19.4% vs. 3.9%; adjusted odds ratio [aOR] 6.0, 95% confidence interval [CI], 3.5-10.3), a NF measurements ≥5 mm (6.5% vs. 0.4%; aOR, 14.8; 95% CI, 5.4-40.1), or hCG adjusted multiples of the median (MoM) ≥ the 95th percentile (10.8% vs. 3.3%; aOR, 3.6; 95% CI, 1.8-7.2). In models that did not consider screen positive grouping, cases were more likely than controls to have NF measurements ≥5 mm, alpha-fetoprotein adjusted MoM≤ the 10th percentile, hCG adjusted MoM ≤25th percentile, and/or hCG adjusted MoM ≥75th percentile. These findings and a previous study by these investigators suggest that second trimester maternal serum biomarkers, together with NF measurement, may be useful indicators of an increased risk of CHD in screen positive pregnancies without identified fetal chromosome abnormalities and indicate the need for fetal echocardiogram.

Gastroschisis: Clinical presentation and associations

Gastroschisis is a major malformation which requires immediate surgical care to return the exposed viscera to the abdominal cavity, parenteral nutrition until bowel motility permits oral feedings, and evaluation for coexisting malformations. Almost all cases are diagnosed prenatally using midtrimester ultrasound and maternal serum alphafetoprotein measurement. This allows most infants to be delivered in a tertiary care facility where the best mode of delivery and neonatal management can be determined. About 10% of infants with gastroschisis will have other malformations. Half of these are considered related to the gastroschisis (intestinal atresia or stenosis, malrotation, cryptorchidism, amyoplasia, urinary tract obstruction). Other associated malformations occur which are not recognized to be secondary to the gastroschisis. Prominent among these are cardiac and limb defects. Fetal and neonatal mortality are increased, but neither appear related to lethal malformations.

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories

Technical standards and guidelines: Prenatal screening for open neural tube defects: This new section on “Prenatal Screening for Open Neural Tube Defects,” together with the new section on “Prenatal Screening for Down Syndrome,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories *

Technical standards and guidelines: Prenatal screening for Down syndrome: This new section on “Prenatal Screening for Down Syndrome,” together with the new section on “Prenatal Screening for Open Neural Tube Defects,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories

Technical standards and guidelines: Prenatal screening for Down syndrome: This new section on “Prenatal Screening for Down Syndrome,” together with the new section on “Prenatal Screening for Open Neural Tube Defects,” replaces the previous Section H of the American College of Medical Genetics Standards and Guidelines for Clinical Genetics Laboratories *

Prevention of Neural Tube Defects by Periconceptional Use of Folic Acid

Prevention of Neural Tube Defects by Periconceptional Use of Folic Acid

Fetal gender impact on multiple-marker screening results

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are used in combination with maternal age to calculate the risk for Down syndrome (DS) in pregnancy. Increased levels of hCG and decreased levels of MSAFP and uE3 are consistent with an increased risk for DS. We retrospectively evaluated second-trimester maternal serum marker levels in a large cohort of patients with known normal outcomes and documented fetal gender. These included 15,428 patients who had MSAFP measurements, 11,428 patients with both MSAFP and hCG, and 6,090 patients with all three markers including uE3. MSAFP levels in patients with female fetuses were consistently lower than those with males. Conversely, hCG was higher in pregnancies with females as compared to males. No gender-related difference was noted for uE3. These results would suggest that the computed DS risk for female fetuses is higher than for males, despite the fact that the incidence of DS is similar in both genders. This information could be useful for calculating gender-specific DS risk; however, this would require ultrasonographic determination of fetal sex.

Teratogenicity of High Vitamin A Intake

Rothman, Kenneth J.; Moore, Lynn L.; Singer, Martha R.; Nguyen, Uyen-Sa D. T.; Mannino, Salvatore; Milunsky, Aubrey Author Information

Teratogenicity of high vitamin A intake.

Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest. Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest. For defects associated with cranial-neural-crest tissue, the ratio of the prevalence among the babies born to women who consumed more than 15,000 IU of preformed vitamin A per day from food and supplements to the prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 10,000 IU per day to that among the babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation. High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.

Impact of prenatal mid-trimester screening on the prevalence of fetal structural anomalies: a prospective epidemiological study.

The objective of this study was to evaluate the effectiveness of the measurement of maternal serum alpha-fetoprotein (MSAFP) at 16 weeks and a subsequent routine ultrasound screening at 18-20 weeks' gestation and the impact on the birth prevalence of congenital structural anomalies in an unselected pregnant population of Hungary in a prospective epidemiological study. A total of 63,794 pregnant women (representing one-sixth of the population of Hungary) were offered this screening program over 3 years (1988-90). Of the pregnant population, 75.7% (48,312) received MSAFP screening and in 81.0% (51,675), at least one ultrasound scan was performed. In the screened pregnancies, 496 craniospinal, thoraco-abdominal, urogenital and other severe major anomalies occurred; 317 were detected at 18-20 weeks (sensitivity 63.1%; specificity 100.0%; positive predictive value 100.0%). The sensitivity of ultrasound scanning was significantly higher (p < 0.05) than that of the MSAFP screening. (At the time of ultrasound scanning the MSAFP value was known.) In this study, the less serious anomalies such as hydrocele, hypospadias and undescended testicle were not systematically searched for, but the birth prevalences were calculated. The overall mid-trimester prevalence of severe plus less severe major anomalies was 2.26%. The birth prevalences of severe major anomalies were 0.57 (craniospinal), 4.36 (thoracoabdominal and urogenital) and 1.21 (other severe) per 1000. These values were lower than the mid-trimester prevalences which were 2.94, 5.20 and 2.06 per 1000, respectively. The prevalence values at the age of 1 year were also calculated (0.36, 2.21, 0.54 per 1000, respectively). We conclude that our screening program with availability of termination of pregnancy could significantly (p < 0.05) reduce the prevalence of severe major abnormalities at birth. Training programs in cardiac scanning are required.

Decreased alpha-fetoprotein in amniotic fluid and maternal serum in diabetic pregnancy

To determine a reference level for alpha-fetoprotein (AFP) in the amniotic fluid (AF) in pregnant women with insulin-dependent diabetes mellitus in order to suggest an explanation for the observed decrease in maternal serum AFP.Alpha-fetoprotein was measured in AF, maternal serum, or both in the second trimester in 287 pregnant women with insulin-dependent diabetes mellitus. Retrospectively, these AFP values were correlated with glycosylated hemoglobin (HbA1C) levels, early fetal growth delay, and congenital malformations.The median concentration of AFAFP was 0.89 multiples of the normative median (MoM) (n = 280; 95% confidence interval [CI] 0.88-0.93 MoM); the maternal serum AFP (MSAFP) value was 0.78 MoM (n = 155; 95% CI 0.77-0.84 MoM). A statistically significant but weak positive correlation was found between HbA1C and MSAFP (r2 = 0.033, P = .03), but the correlation with AFAFP was not statistically significant. The levels of AFP did not correlate with early fetal growth delay. One neural tube defect, but none of the 11 other major malformations, was detected by AFP screening.A physiologic basis for the decreased AFAFP and MSAFP levels is still obscure. Screening for congenital malformations in diabetic pregnancies should include both a mid-gestation ultrasound scan and MSAFP measurement. However, routine amniocentesis does not seem to be indicated. Concentrations of AFAFP may be corrected for the observed decrease.

Current issues in maternal serum alpha-fetoprotein screening.

Measurement of maternal serum alpha-fetoprotein originated in the early 1970s as a means to screen for fetal neural tube defects, a relatively common and devastating class of malformations. Since that time, assay methods have improved, interpretation has been refined, follow-up testing for neural tube defects has advanced, and many other disease associations have been uncovered. It is a unique test, both in its clinical application and its laboratory implementation. The present review outlines current procedures for maternal serum alpha-fetoprotein screening and summarizes recent developments.

273 Alphafetoprotein in Diabetic Pregnancy-A Reassessment

We correlated glycosylated hemoglobin (HbA1) with maternal serum alpha-fetoprotein (MSAFP) in 92 and amniotic fluid AFP (AFAFP) in 27 patients with pregestational and gestational diabetes. MSAFP and AFAFP were measured between 15 and 20 weeks and correlated with HbA1. In group 1, HbA1 was measured at < or = 12 weeks' gestation; in group 2, it was measured 0-6 weeks before MSAFP measurement; and in group 3, it was measured within 6 weeks after MSAFP. Mean MSAFP was 1.02 +/- 0.77 multiples of the median (MOM) (+/- SD) in all diabetics, 1.1 +/- 0.93 MOM in gestational diabetics and 0.89 +/- 0.33 MOM in pregestational diabetics (P = NS). There was no correlation between MSAFP and HbA1 in groups 1-3. Patients with HbA1 > 9 g% had a mean MSAFP of 0.84 MOM as compared to 0.85 MOM in those with HbA1 < 9 g% (P = NS). AFAFP values were within normal limits even in patients with HbA1 > 9 g% in early pregnancy (n = 8). No significant decrease in MSAFP was seen in pregestational diabetics, and no correlation was seen with HbA1 levels. AFAFP levels were unchanged in diabetics.

Combining maternal serum alpha-fetoprotein measurements and age to screen for down syndrome in pregnant women under age 35

Combining maternal serum alpha-fetoprotein measurements and age to screen for down syndrome in pregnant women under age 35