Elevated Maternal Serum Alpha-fetoprotein Research Articles

Cephalocele detection in utero: sonographic and clinical features.

Sonographic and clinical features of 26 fetal cephaloceles were reviewed retrospectively. The most frequent reason for referral was elevated maternal serum alpha-fetoprotein levels. The smallest lesion identified was 0.4 x 0.5 cm (frontal, at 20 weeks); the largest was 9.0 x 10.0 cm (frontal, at 27 weeks). Twenty-four of 26 cephaloceles were detected on prenatal ultrasound examination; in 13 of these, more than 50% of the intracranial contents were exteriorized. Fifteen of 24 cephaloceles detected prenatally had a sulcal pattern (identified between 16 and 36 weeks' gestation); five were solid without a sulcal pattern (identified between 13 and 21 weeks' gestation), three were cystic, and one underwent a change in appearance from solid at 21 weeks to cystic at 26 weeks. Other cranial features were evaluated and included visible skull defect, seen in 23/24 (96%), ventriculomegaly, in 6/26 (23%); microcephaly, in 12/24 (50%); beaked tectal plate, in 6/16 (38%); and flattened basiocciput, in 9/24 (38%). Of the 26 cases, 14 had normal amniotic fluid volume, five had oligohydramnios and seven had polyhydramnios. Fetuses with oligohydramnios had the highest incidence of concurrent fetal abnormalities; four of five fetuses (80%) with oligohydramnios had additional structural abnormalities. In the overall population, a very high incidence of other abnormalities was found; 17/26 (65%) cases showed additional abnormalities, some of which were not detected by ultrasound. Five fetuses had Meckel-Gruber syndrome and three had amniotic band syndrome. Only one of the 18 karyotypes obtained was abnormal (trisomy 18). Survival was very poor; only two of the eight who survived until birth are currently living.

Abnormal uterine artery doppler velocimetry predicts adverse obstetric outcome in women with elevated maternal serum alphafetoprotein (MSAFP): [formula omitted]∗, I.M. Bernstein, E.L. Capeless, Dept. Ob/Gyn, Univ. of VT., Burl., VT

Abnormal uterine artery doppler velocimetry predicts adverse obstetric outcome in women with elevated maternal serum alphafetoprotein (MSAFP): [formula omitted]∗, I.M. Bernstein, E.L. Capeless, Dept. Ob/Gyn, Univ. of VT., Burl., VT

Association of ultrasound placental abnormalities with elevated maternal serum alpha-fetoprotein and pregnancy outcome: [formula omitted], Y. Pan, S.G. Pinette, D. Abel, J. Blackstone. Dept. Ob/Gyn, Maine Medical Center, Portland, ME

Association of ultrasound placental abnormalities with elevated maternal serum alpha-fetoprotein and pregnancy outcome: [formula omitted], Y. Pan, S.G. Pinette, D. Abel, J. Blackstone. Dept. Ob/Gyn, Maine Medical Center, Portland, ME

Parent preferences and prenatal testing for neural tube defects.

Previous analyses of prenatal screening for neural tube defects have generally found benefits to exceed costs. The usual screening battery follows an elevated maternal serum alpha-fetoprotein level with high-resolution ultrasound and/or amniocentesis. Current thinking focuses on weighing the risk of a false-negative (an abnormality missed) against the risk of an amniocentesis-induced fetal loss. This thinking neglects the risk of a false-positive (an unaffected fetus labeled abnormal) and individual parents' preferences concerning a false-negative vs a fetal loss. With these risks included, we find that high-resolution ultrasound is appropriate for all women with elevated serum alpha-fetoprotein. Women with moderately elevated serum alpha-fetoprotein who have negative ultrasound scans need no further testing, nor do women with highly elevated serum alpha-fetoprotein and positive ultrasound scans. Further testing using amniocentesis to confirm the ultrasound result is appropriate for women with moderately elevated serum alpha-fetoprotein and positive ultrasound scans, and for women with highly elevated serum alpha-fetoprotein and negative ultrasound scans. The actual cutoffs defining normal, moderately elevated, and highly elevated serum alpha-fetoprotein depend on several parameters, particularly the underlying prevalence of neural tube defects and the parents' preferences.

MSAFP levels and oesophageal atresia

This study was undertaken to evaluate the relationship between maternal serum alpha-fetoprotein (MSAFP) levels and oesophageal atresia (OA). OA occurred in 16 fetuses of mothers who had an MSAFP test in the study interval. The multiple of the median (MOM) value for MSAFP averaged 1.54 +/- 0.65 (range 0.5-2.9 MOM), which was significantly higher than the value seen in controls. The median MOM was 1.35. Using a cut-off of 2.5 MOM, the sensitivity of MSAFP for detecting OA was 19 per cent. Although OA should be considered in the differential diagnosis of an elevated MSAFP level, MSAFP cannot be considered an appropriate screening test for OA given the low sensitivity.

Midtrimester hemoperitoneum caused by placenta percreta in association with elevated maternal serum α-fetoprotein level

We report a case of hemoperitoneum in the second trimester due to placenta percreta which was associated with an elevated maternal serum alpha-fetoprotein. A 29-year-old woman, gravida 4, para 1-0-2-1, was seen at 17 weeks' gestation with an acute abdomen. Maternal serum alpha-fetoprotein in a sample drawn 1 week previously revealed a value of 5.0 multiples of the median. At laparotomy, placenta percreta was discovered. This case of placenta percreta diagnosed in the second trimester was associated with an elevated maternal serum alpha-fetoprotein level. Physicians counseling patients with unexplained elevated maternal serum alpha-fetoprotein levels should include placenta accreta or percreta in the differential diagnosis and should maintain an awareness of its existence in patients with acute abdomen in pregnancy.

The effect of fetomaternal bleeding on the risk of adverse pregnancy outcome in patients with elevated second-trimester maternal serum α-fetoprotein levels

Unexplained maternal serum alpha-fetoprotein elevation has been associated with an increased risk of intrauterine growth retardation, preterm delivery, and intrauterine fetal death. The purpose of this study was to determine whether patients with evidence of recent fetomaternal bleeding as a cause of elevated maternal serum alpha-fetoprotein level are at a lower risk for adverse pregnancy outcome than those without such evidence. Patients with elevated maternal serum alpha-fetoprotein levels who had a singleton viable fetus without ultrasonographically detectable anomalies were offered inclusion in this study. Study participants had blood drawn for fetal cell analysis before amniocentesis. The pregnancy outcomes of patients with evidence of fetomaternal bleeding were compared with those of patients without. Of 229 patients, 109 (47.6%) had evidence of fetomaternal bleeding as a possible cause of elevated maternal serum alpha-fetoprotein. Of these, 86 (78.9%) had a normal pregnancy outcome compared with 84 of 120 (70.0%) with a negative stain for fetal cells (p not significant). There was no significant difference in the incidence of preterm delivery (14 [12.8%] vs 15 [12.5%]), intrauterine growth retardation (5 [4.6%] vs 9 [7.5%]), or intrauterine fetal death (4 [3.7%] vs 8 [6.6%]) when patients with a positive stain for fetal cells were compared with those with a negative stain. Among patients with elevated maternal serum alpha-fetoprotein levels, those with evidence of recent fetomaternal bleeding do not appear to be at decreased risk for adverse pregnancy outcome compared with those without such evidence.

Genetic counseling for a family with two distinct anomalies: a case report of a neural tube defect and 5p- syndrome in a fetus.

AbstractA couple presented for genetic counseling because of an elevated maternal serum alpha fetoprotein. Ultrasound examination revealed the presence of a neural tube defect. The couple declined an amniocentesis, but chose serial ultrasound evaluations instead. Ultrasounds eventually identified microcephaly, but the couple continued to decline amniocentesis. After the child's birth, the diagnosis of 5p‐ syndrome was made. The couple's decision not to have an amniocentesis allowed the family their right to autonomy; however, prenatal chromosome analysis would have provided this couple with a great deal more prognostic information. We discuss the conflict between a counselor's duty to respect a client's freedom vs. duty to care for a client's welfare. We address issues of nondirective counseling and the need for more studies looking at the decision‐making process in prenatal diagnosis.

Screening maternal serum alpha-fetoprotein levels and human parvovirus antibodies.

The association between gestational infection with human parvovirus (B19) and fetal loss has increased interest in this virus and demand for diagnostic testing. However, serological assays for B19 are not yet widely available. Maternal serum alpha-fetoprotein (MSAFP) testing is commonly used during the second trimester to screen for various fetal defects. We attempted to determine whether an elevated level of MSAFP would be an appropriate indication for B19-specific tests. Over a 26-month period, MSAFP tests were performed at Michigan State University for 21 392 women. Sera remaining after that testing were stored frozen. Of these, 22 cases samples--from women with MSAFP levels greater than 3.0 multiples of the median (MOM) and pregnancies that ended in fetal loss--and 44 matched control samples--from women with MSAFP levels greater than 0.4 and less than 2.2 MOM and live births at term--were tested for B19 antibodies. None of the 66 samples was IgM positive, while 33 (50 per cent) were IgG positive. The presence of IgG was not significantly associated with case or control status (matched odds ratio = 0.77, 95 per cent confidence interval 0.28-2.11). These findings are consistent with other studies indicating prior infection in approximately half of adults and suggest that elevated screening MSAFP levels, in the absence of other evidence of B19 infection, should not prompt B19-specific testing.

Life without amniocentesis: elevated maternal serum alpha-fetoprotein in the Manitoba program 1986-91.

Pregnant women demonstrating an elevated maternal serum alpha-fetoprotein level are at increased risk for fetal neural tube defect or other anomaly. Diagnostic procedures to evaluate these pregnancies include high-resolution ultrasound and amniocentesis to measure amniotic fluid levels of alpha-fetoprotein and N-acetylcholinesterase. We wished to examine the efficacy of detailed ultrasound examination alone, in evaluation of women with 'unexplained' elevation of maternal serum alpha-fetoprotein. The results showed that no neural tube defects were missed in the assessment of 1325 pregnancies with a raised level of maternal serum alpha-fetoprotein over 6 years, despite complete reliance on ultrasound in 98%. Detailed fetal ultrasound evaluation by experienced personnel is adequate to identify all cases of neural tube defects in a selected high-risk population.

Maternal serum alpha-fetoprotein levels in chorioangiomas.

It has been suggested that chorioangiomas should be added to the list of causes of elevated maternal serum alpha-fetoprotein levels. We undertook a review of maternal serum alpha-fetoprotein levels in chorioangiomas histologically diagnosed in our department, and a review of the literature. Maternal serum alpha-fetoprotein level was elevated in only 1 of our 11 cases of chorioangioma. To date, there have been 14 case reports of chorioangiomas in which maternal serum alpha-fetoprotein levels have been recorded; 12 of these were associated with elevated maternal serum alpha-fetoprotein levels. We consider that, although chorioangiomas may be a cause of elevated maternal serum alpha-fetoprotein levels, it is likely to be infrequently a cause of such elevations in our population.

Elevated MSAFP levels and congenital heart defects: lack of an association.

This study was undertaken to evaluate the relationship between elevated maternal serum alpha fetoprotein (MSAFP) levels and congenital heart defects. Thirty-two infants with isolated major congenital heart defects and whose mothers had had MSAFP screening were identified. In only one case was the MSAFP greater than 2.3 multiples of the median. A review of our experience with women with elevated MSAFP levels did not document a higher rate of congenital heart malformations than would be expected based on estimated frequencies in the general population.

Association of Antinuclear and Antiphospholipid Antibodies with Unexplained Elevations of Maternal Serum Alpha-Fetoprotein

We hypothesized that antinuclear antibodies (ANA) and antiphospholipid antibodies (APLA) are a common etiology for midtrimester unexplained elevations of maternal serum alpha-fetopro-tein (MSAFP) and that their presence may correlate with perinatal outcome. Sixty-eight patients with unexplained elevations of MSAFP were identified and screened for the presence of ANA and APLA, then prospectively followed. Perinatal outcome was compared between patients with and without autoantibodies. Of the study population 39.7% had evidence of autoantibody formation. When compared to patients without autoantibodies, these patients exhibited higher mean multiples of the median for MSAFP and significantly higher perinatal morbidity. We conclude that the presence of autoantibodies in association with unexplained elevations of MSAFP seems to identify a group of pregnancies at increased risk for perinatal morbidity.

Circulating intercellular adhesion molecule-1 in amniotic fluid, maternal serum α-fetoprotein levels, and intrauterine growth retardation

Our purpose was to determine if circulating intercellular adhesion molecule-1, a marker of chronic inflammation, is present in amniotic fluid in midtrimester, is increased in patients with elevated maternal serum alpha-fetoprotein level, and is associated with intrauterine growth retardation. Amniotic fluid circulating intercellular adhesion molecule-1 levels were assayed by enzyme-linked immunoassay in 273 samples obtained by midtrimester amniocentesis in gestations involving a single, structurally normal fetus. The control group consisted of 108 patients with normal maternal serum alpha-fetoprotein levels and 165 patients with elevated levels. Intrauterine growth retardation was diagnosed if birth weight was < 10th percentile for the clinically estimated gestational age. Circulating intercellular adhesion molecule-1 was detectable in amniotic fluid in 105 of 273 samples (38%). In the control group it was detectable in amniotic fluid in seven of 108 (6%). In patients with elevated maternal serum alpha-fetoprotein 97 of 164 (59%) had detectable levels (p < 0.001). Of the 273 cases 38 (14%) had intrauterine growth retardation. Of these 23 (59%) had detectable circulating intercellular adhesion molecule-1 levels (p < 0.001). Of the seven cases of intrauterine growth retardation with normal maternal serum alpha-fetoprotein levels, one (14%) had detectable circulating intercellular adhesion molecule-1. Of the 31 cases of intrauterine growth retardation with elevated maternal serum alpha-fetoprotein 22 (71%) had detectable circulating intercellular adhesion molecule-1. When circulating intercellular adhesion molecule-1 was detectable in amniotic fluid, increasing levels was significantly related to decreasing gestational age at delivery (p < 0.005). Midtrimester amniotic fluid from normal pregnancies does not generally contain detectable circulating intercellular adhesion molecule-1. Detectable amniotic fluid levels are significantly related to a birth weight < 10th percentile at delivery and to elevated midtrimester maternal serum alpha-fetoprotein levels. Increasing circulating intercellular adhesion molecule-1 levels are related to shortened length of gestation. This test may contribute to risk assessment for intrauterine growth retardation and prematurity. Circulating intercellular adhesion molecule-1 is a known marker of inflammatory processes; its further study may also improve understanding of the pathophysiologic mechanisms of certain cases of intrauterine growth retardation and prematurity.

Value of maternal serum alpha-fetoprotein levels of 5.0 MOM or greater and prenatal sonography in predicting fetal outcome.

To determine fetal outcomes and the capability of sonography to help predict these outcomes in patients with maternal serum alpha-fetoprotein (MSAFP) levels of 5.0 multiples of the median or greater. Real-time sonography was performed in patients with singleton and multiple gestations. After sonography, the pregnancy was monitored. Inaccurate historical dating caused elevated MSAFP levels in 14 patients. In the remaining 72 singleton gestations, 42 fetuses (58%) had anomalies, 13 (18%) died in utero or after birth, three (4%) had intrauterine growth retardation or were premature, and 14 (19%) were normal, with no complications. A poor outcome occurred in 58 (80%) of the singleton pregnancies, and sonography depicted an abnormality in 49 (84%) of these patients. Most pregnant patients with MSAFP levels of 5.0 MOM or greater have an unfavorable outcome. Sonography depicts most of these abnormal pregnancies.

First‐trimester biochemical screening for fetal chromosome abnormalities and neural tube defects

Alpha-fetoprotein (AFP), unconjugated oestriol (UE3), intact human chorionic gonadotrophin (intHCG), and the free beta subunit of chorionic gonadotrophin (F beta HCG) were investigated in a series of 21 chromosomally abnormal and 14 open neural tube defect pregnancies ascertained from a series of 14,000 prospectively collected maternal serum samples at 6-14 weeks' gestation. In 16 cases of Down's syndrome, significant reductions were found for AFP (0.65 multiples of the normal median) and UE3 (0.67 MOM). IntHCG levels were unaltered (0.97 MOM) but a significant increase was found for F beta HCG (1.96 MOM). Significant correlations were found for AFP and UE3 in the controls and for intHCG and F beta HCG in both the control and the Down's syndrome pregnancies. In a group of five trisomy 18 pregnancies, median MOMs were for AFP 0.71, for UE3 0.34, for intHCG 0.27, and for F beta HCG 0.15. None of 13 pregnancies with open neural tube defects at 8-13 weeks gestation had elevated maternal serum AFP levels, whereas matched second-trimester samples from the same pregnancies at 16-18 weeks gestation all had significantly elevated AFP levels. Thus, biochemical screening for chromosome abnormalities may be practicable in the first trimester using free beta human chorionic gonadotrophin in combination with AFP and maternal age. However, a separate screening protocol using AFP at 15-18 weeks gestation would still be required for effective detection of neural tube defects.

Presented by invitation at the Fifty-ninth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Ojai, California, October 11-18, 1992.

Unexplained elevations in maternal serum alpha-fetoprotein in the midtrimester are associated with adverse pregnancy outcome. Recently it has also been suggested that elevations of maternal serum human chorionic gonadotropin in the second trimester may be associated with adverse pregnancy outcome. We conducted a cohort study of 460 women at Swedish Medical Center, Seattle, Washington, between Jan. 1, 1990, and Aug. 15, 1991, inclusive. Entry criteria for the cohort included (1) triple screen analysis (maternal serum alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol) between 15 and 18 weeks' gestation, (2) a risk for Down syndrome of more than one in 195 on the basis of triple screen analysis, (3) study group human chorionic gonadotropin > or = 2 multiples of the median and referent group < or = 2 multiples of the median, alpha-fetoprotein < or = 2 multiples of the median, unconjugated estriol > or = 0.5 multiples of the median, and (4) chromosomally normal single gestation without anomalies. Cumulative incidence risk ratios were estimated for each pregnancy outcome as a measure of the relative association with elevated human chorionic gonadotropin (> or = 2.0 multiples of the median) and adverse pregnancy outcome: low birth weight, < or = 2500 gm; preterm delivery, < 37 weeks' gestation; and small for gestational age, < or = 10th percentile. The Mantel extension test was used to evaluate any apparent linear trend in risk between level of human chorionic gonadotropin and adverse pregnancy outcome. Elevated human chorionic gonadotropin levels were associated with an increased risk for low birth weight (relative risk = 4.0), preterm delivery (relative risk = 2.8), and small for gestational age (relative risk = 1.8). The risk for each adverse outcome increased with increasing levels of human chorionic gonadotropin. Elevations of human chorionic gonadotropin in the midtrimester appear to be associated with adverse pregnancy outcome. The magnitude of the risk correlates with the level of human chorionic gonadotropin. This risk appears to be independent of the risk for adverse pregnancy outcome associated with unexplained elevations of maternal serum alpha-fetoprotein.

Maternal serum biochemical markers in pregnancies with fetal parvovirus B19 infection

Hydrops fetalis and fetal death caused by fetal parvovirus B19 infection have been reported to be associated with elevated maternal serum alpha-fetoprotein (AFP), based on a total of six cases. It has been suggested that the absence of AFP elevation may be reassuring. Maternal serum levels of the Down syndrome screening markers unconjugated oestriol and human chorionic gonadotropin in cases of fetal parvovirus infection have not been previously reported. We report four cases of hydrops fetalis and fetal death caused by fetal parvovirus infection, each with unremarkable second-trimester levels of AFP, unconjugated oestriol, and human chorionic gonadotropin.

Prenatal sonographic diagnosis of placental infarction in association with elevated maternal serum alpha-fetoprotein

Prenatal sonographic diagnosis of placental infarction in association with elevated maternal serum alpha-fetoprotein

Chorionic villus sampling followed by amniocentesis in the same pregnancy.

In our consecutive series of 2,574 chorionic villus sampling (CVS) patients, 146 women (5.7%) underwent a subsequent amniocentesis in the same pregnancy for the indications of absent or insufficient villi (3.3%), elevated maternal serum alpha-fetoprotein (0.93%), CVS mosaicism (0.89%), culture failure (0.23%), specimen contamination (0.15%), and CVS aneuploidy (0.12%). Patients presenting for a CVS should be informed of the possible need for a subsequent amniocentesis in the same pregnancy. There is a need for individual prenatal diagnosis programs to analyze their own data and provide genetic counseling information which pertains specifically to their institution.