The impact of MSAFP screening on genetic services, 1984–1986

The impact of maternal serum alpha-fetoprotein (MSAFP) screening on genetic centers was investigated by a questionnaire mailed to 220 genetic centers in the United States. Eighty-four (38%) of centers responded to the questionnaire; of these (34%) were adequate for analysis. About 33% of the programs performed their own MSAFP testing. Approximately 70% of centers used 2.5 times the median (MoM) as a cutoff for MSAFP elevations and approximately 75% of centers used a sliding cutoff for low MSAFP based on both maternal age and the multiple of the median. Between 1984 and 1986, the total number of women screened by the reporting centers increased by about 4.7 fold. The percentage of women seen in their centers for prenatal counseling due to high or low MSAFP levels increased from 1.3% in 1984 to 13.1% in 1986. The percentage of prenatal diagnoses utilizing amniocentesis for high or low MSAFP increased from 3% in 1984 to 10% in 1986. During this period, 76 cases of Down syndrome were detected based on low MSAFP; this represents 1.7% of amniocenteses for low MSAFP. These data demonstrate a significant increase in the number of women seen for prenatal counseling and amniocentesis at the reporting genetic centers and is likely to represent a similar trend at all genetic centers. The impact of high MSAFP screeing for neural tube defects and low MSAFP screening for Down syndrome is likely to increase over the coming years and genetic programs should prepare for the increasing utilization of services necessary to handle women with high and low MSAFP levels.     

The impact of MSAFP screening on genetic services, 1984-1986

The impact of maternal serum alpha-fetoprotein (MSAFP) screening on genetic centers was investigated by a questionnaire mailed to 220 genetic centers in the United States. Eighty-four (38%) of centers responded to the questionnaire; of these (34%) were adequate for analysis. About 33% of the programs performed their own MSAFP testing. Approximately 70% of centers used 2.5 times the median (MoM) as a cutoff for MSAFP elevations and approximately 75% of centers used a sliding cutoff for low MSAFP based on both maternal age and the multiple of the median. Between 1984 and 1986, the total number of women screened by the reporting centers increased by about 4.7 fold. The percentage of women seen in their centers for prenatal counseling due to high or low MSAFP levels increased from 1.3% in 1984 to 13.1% in 1986. The percentage of prenatal diagnoses utilizing amniocentesis for high or low MSAFP increased from 3% in 1984 to 10% in 1986. During this period, 76 cases of Down syndrome were detected based on low MSAFP; this represents 1.7% of amniocenteses for low MSAFP. These data demonstrate a significant increase in the number of women seen for prenatal counseling and amniocentesis at the reporting genetic centers and is likely to represent a similar trend at all genetic centers. The impact of high MSAFP screening for neural tube defects and low MSAFP screening for Down syndrome is likely to increase over the coming years and genetic programs should prepare for the increasing utilization of services necessary to handle women with high and low MSAFP levels.     

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) lavels 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. © 1994 Wiley-Liss, Inc.     

Combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low estriol is highly predictive of anencephaly

Increased levels of second trimester maternal serum alpha-fetoprotein (MSAFP) have long been established as a marker for neural tube defects (NTDs). In addition, decreased levels of maternal estriol in the third trimester have been reported in pregnancies with anencephalic fetuses. The purpose of this study was to evaluate whether early second trimester unconjugated serum estriol (uE3) is an independent predictor of NTDs. The study included 57,031 patients who underwent maternal serum screening with MSAFP at 14–22 weeks gestation. Of these, 23,415 also had uE3 measurements. There were 63 cases of NTD, an overall incidence of 1.1 per 1,000. Elevated MSAFP (≥2.5 MOM) was detected in 1,346 patients, 48 of which had NTDs. Decreased uE3 (≤0.5) was detected in 1,437 patients, 17 of which had NTDs. The incidence of NTDs was significantly higher in patients with low uE3, compared to patients with normal/high uE3 (1.15% vs. 0.09%, P < 001). Finally, 51 patients had both increased MSAFP and decreased uE3; 16 of these had NTDs, 14 of which were anencephalics. In conclusion, both elevated MSAFP and low maternal serum estriol are predictive of NTD but have a low sensitivity. The combination of abnormally elevated MSAFP and low estriol is highly predictive of NTD in particular anencephaly. Am. J. Med. Genet. 75:297–299, 1998. © 1998 Wiley-Liss, Inc.     

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. Am. J. Med. Genet. 76:369–371, 1998. © 1998 Wiley-Liss, Inc.     

Low maternal serum alpha-fetoprotein levels and congenital diaphragmatic defects

We report on 2 cases of fetal congenital diaphragmatic defects with normal chromosomes among 105 patients referred for evaluation for low maternal serum alpha-fetoprotein (MSAFP) levels. The mechanism for this striking association is not clear. The association of low MSAFP levels and congenital diaphragmatic defects may have importance for MSAFP screening programs.     

Characteristics of women who refuse an offer of prenatal diagnosis: Data from the California maternal serum alpha fetoprotein blood test experience

This paper presents data from the California maternal serum alpha fetoprotein (MSAFP) program in order to explore the effect and interaction of various factors, especially ethnicity, abortion history and attitudes, religion, and religiosity on MSAFP test decision. The intent is to describe which women are more likely to reject MSAFP screening and also to understand the reasons for refusal and the meanings associated with it. We obtained data on sociodemographics and reproductive history from 595 obstetrical patient charts; we conducted semistructured interviews with an additional 158 pregnant women who were European-American, English-speaking Latina, or Spanish-speaking Latina. All of the women had been offered screening within the context of California's MSAFP Program. We found that women who had never terminated a pregnancy, Spanish-speaking Latinas, and women who scored high on a religiosity scale were significantly more likely to refuse testing. However, we found that all of those factors were strongly mediated by the effects of ethnicity and acculturation, producing different patterns of association in different groups of women. Am. J. Med. Genet. 78:433–445, 1998. © 1998 Wiley-Liss, Inc.     

Low material serum alpha-fetoprotein levels and congenital diaphragmatic defects

We report on 2 cases of fetal congenital diaphragmatic defects with normal chromosomes among 105 patients referred for evaluation for low maternal serum alpha-fetoprotein (MSAFP) levels. The mechanism for this striking association is not clear. The association of low MSAFP levels and congenital diaphragmatic defects may have importance for MSAFP screening programs.     

母血AFP和胎儿大脑中动脉收缩期血流峰值对评估胎儿贫血的作用

目的: 探讨胎儿宫内贫血母血AFP(MSAFP)水平和胎儿大脑中动脉收缩期血流峰值(MCA-PSV)的相关性并用胎儿血红蛋白(FHB)值验证其相关性,评价MSAFP和MCA-PSV对胎儿贫血病例的临床预测和监护意义。方法: 对32例怀疑有胎儿贫血病例(自体免疫性胎儿贫血4例, 地中海贫血11例,B19微小病毒感染10例,胎盘血管瘤7例)进行55次MSAFP和MCA-PSV测量,对于MCA-PSV异常病例抽取脐带血,共获得19份胎儿血液标本,测定FHB含量。结果: MSAFP与MCA-PSV有相关性(n=55,r=0.57,P<0.01)。19例胎儿血标本检查共15例贫血标本,其中4例假阳性病例的MSAFP正常。贫血胎儿的MSAFP明显高于非贫血胎儿,地中海贫血和免疫溶血性贫血病例MSAFP升高比MCA-PSV升高早15-20 d,B19病毒感染和胎盘血管瘤导致的贫血病例MSAFP升高则比MCA-PSV晚10-12 d(P<0.05)。MSAFP(r=-0.87)和MCA-PSV(r=-0.67)与FHB水平有相关性。结论: 胎儿宫内贫血时MSAFP水平升高的时间和程度比MCA-PSV的变化更具有预测和监护意义,而且两者间呈相关性。因此,MSAFP和MCA-PSV可能是临床预测和监护不同程度胎儿宫内贫血最有价值的联合测量指标。     

Uterine artery Doppler velocimetry in the prediction of adverse obstetric outcomes in unexplained MSAFP elevations

Unexplained maternal serum-fetoprotein (MSAFP) elevation has been known to be associated with adverse obstetric outcomes, however it is not sufficiently useful as a screening test. This study was undertaken to determine whether uterine artery Doppler velocimetry could define a subset of patients with an elevated MSAFP level in whom complications of pregnancy might develop. The subjects included 179 women between 26 and 28 weeks' gestation with MSAFP > or = 2.5 multiples of the median, in whom either the presence of an early diastolic notch or a resistance index 0.6 was considered as an abnormal Doppler velocimetry finding. Those subjects who displayed abnormal Doppler velocimetry findings showed an increased incidence of preeclampsia, preterm birth, IUGR, and IUFD compared to those subjects with only elevated MSAFP (p < 0.05). No differences were observed in the incidence of LBW. Positive predictive values of adverse obstetric outcomes were significantly higher in the group having both elevated MSAFP and abnormal Doppler velocimetry compared to the group with only elevated MSAFP (p < 0.05). Uterine artery Doppler velocimetry in the second trimester can improve the value of unexplained MSAFP elevation in the prediction of adverse obstetric outcomes.     

Effect of adjustment of maternal serum α-fetoprotein levels in insulin-dependent diabetes mellitus

Our objective was to determine the effect of the 20% upward adjustment of maternal serum alphafetoprotein (MSAFP) in patients with insulin-dependent diabetes mellitus (IDDM) on the number of patients that would be classified at increased risk for pregnancy complicated by either Down syndrome (DS) or neural tube defect (NTD). We retrospectively evaluated a database containing 63,110 patients who underwent multiple serum marker screening between 14 and 22 weeks gestation; 620 patients with IDDM had measurements of MSAFP of which 479 also had measurements of β-HCG, allowing calculation of DS risk. Increased NTD risk was defined as MSAFP >2.5 MOM while increased DS risk was defined as a calculated risk ≥1/270. One IDDM patient delivered an infant with a NTD; it was not detected on serum screening. No infants were born with DS. Of the 620 patients with MSAFP determinations, 9 had values >2.5 MOM before adjustment. After upward adjustment, 7 additional patients were identified. Sixteen patients were identified at increased risk for DS before and after adjustment. Our data suggest that the 20% upward adjustment of MSAFP increases by 78%, the number of patients who would require further evaluation for NTD's. Although we were able to identify 620 women with IDDM who underwent serum screening for NTD, the low prevalence of NTD's did not allow us to demonstrate an increased detection rate. The effect of upward adjustment of MSAFP on the number of patients categorized at increased DS risk appears to be minimal. Am. J. Med. Genet. 75:176–178, 1998. © 1998 Wiley-Liss, Inc.     

Maternal serum alpha-fetoprotein screening for Down syndrome: economic considerations

The economic consequences of using an index of maternal age and maternal serum alpha-fetoprotein (MSAFP) screening to indicate risk of Down syndrome (DS) are examined. If DS screening indicated solely by a given maternal age is economically justifiable, then amniocentesis indicated by a DS risk equivalent to that maternal age cutoff, but based on an index of maternal age (for ages below the cutoff) and low MSAFP results, is also economically justifiable. It is concluded that the extant use of MSAFP screening for DS is a move toward the cost-effective use of scarce resources that can be made available with coordinated planning. However, increased professional and public awareness may result in significant increases in aggregate demand for these services. While MSAFP screening for DS is economically justifiable, there exists some potential for bottlenecks at the aggregate level, and these should be considered in conjunction with recommendations that the technology be adopted on a widespread basis.     

Familial risk of congenital heart defect

The economic consequences of using an index of maternal age and maternal serum alpha-fetoprotein (MSAFP) screening to indicate risk of Down syndrome (DS) are examined. If DS screening indicated solely by a given maternal age is economically justifiable, then amniocentesis indicated by a DS risk equivalent to that maternal age cutoff, but based on an index of maternal age (for ages below the cutoff) and low MSAFP results, is also economically justifiable. It is concluded that the extant use of MSAFP screening for DS is a move toward the cost-effective use of scarce resources that can be made available with coordinated planning. However, increased professional and public awareness may result in significant increases in aggregate demand for these services. While MSAFP screening for DS is economically justifiable, there exists some potential for bottlenecks at the aggregate level, and these should be considered in conjunction with recommendations that the technology be adopted on a widespread basis.     

Maternal serum alpha-fetoprotein screening and fetal chromosome anomalies: is lowering maternal age for amniocentesis preferable?

We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098 patients referred for amniocentesis because of low maternal serum alpha-fetoprotein (MSAFP) to those of 445 patients whose indication was elevated MSAFP and those of 361 patients who had amniocentesis for "maternal anxiety." Autosomal trisomies, sex chromosome aberrations, and various structural rearrangements were detected in all 3 groups and actually exceeded the age-related incidence estimates. The frequency of chromosome anomalies in cases studied because of "maternal anxiety" with no prior screening was similar to that in the group referred for low MSAFP (1.38 and 1.27%, respectively). A relatively higher frequency (2.02%) was detected in the group whose indication was elevated MSAFP. Maternal serum screening is designed primarily to recalculate risk figures for Down syndrome, but not for other major chromosome abnormalities. The concept of prenatal screening for chromosome aberrations must therefore be reevaluated. We think that efforts should be directed at making amniocenteses more accessible to patients who request it. "Lowering" maternal age limits to 30 would encompass a greater proportion of pregnancies at risk and would be a step toward more effective prenatal diagnosis for chromosome abnormalities.     

Maternal serum α-fetoprotein screening and fetal chromosome anomalies: Is lowering maternal age for amniocentesis preferable?

We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098 patients referred for amniocentesis because of low maternal serum α-fetoprotein (MSAFP) to those of 445 patients whose indication was elevated MSAFP and those of 361 patients who had amniocentesis for “maternal anxiety.” Autosomal trisomies, sex chromosome aberrations, and various structural rearrangements were detected in all 3 groups and actually exceeded the age-related incidence estimates. The frequency of chromosome anomalies in cases studied because of “maternal anxiety” with no prior screening was similar to that in the group referred for low MSAFP (1.38 and 1.27%, respectively). A relatively higher frequency (2.02%) was detected in the group whose indication was elevated MSAFP. Maternal serum screening is designed primarily to recalculate risk figures for Down syndrome, but not for other major chromosome abnormalities. The concept of prenatal screening for chromosome aberrations must therefore be reevaluated. We think that efforts should be directed at making amniocenteses more accessible to patients who request it. “Lowering” maternal age limits to 30 would encompass a greater proportion of pregnancies at risk and would be a step toward more effective prenatal diagnosis for chromosome abnormalities.     

Mosaic trisomy 16 ascertained through amniocentesis: Evaluation of 11 new cases

Trisomy 16, once thought to result uniformly in early pregnancy loss, has been detected in chorionic villus samples (CVS) from on-going pregnancies and was initially ascribed to a second, nonviable pregnancy. Prenatally detected trisomy 16 in CVS and its resolution to disomy has led to the re-examination of the viability of trisomy 16. This study evaluates 11 cases of mosaic trisomy 16 detected through second trimester amniocentesis. In 9 of the 11 cases, amniocenteses were performed in women under the age of 35 because of abnormal levels of maternal serum alpha-fetoprotein (MSAFP) or maternal serum human chorionic gonadotropin (MShCG). The other two amniocenteses were performed for advanced maternal age. Five of the 11 pregnancies resulted in liveborn infants, and six pregnancies were electively terminated. The liveborn infants all had some combination of intrauterine growth retardation (IUGR), congenital heart defects (CHD), or minor anomalies. Two of them died neonatally because of complications of severe congenital heart defects. The three surviving children have variable growth retardation, developmental delay, congenital anomalies, and/or minor anomalies. In the terminated pregnancies, the four fetuses evaluated by ultrasound or autopsy demonstrated various congenital anomalies and/or IUGR. Cytogenetic and fluorescent in situ hybridization studies identified true mosaicism in 5 of 10 cases examined, although the abnormal cell line was never seen in more than 1% of cultured lymphocytes. Placental mosaicism was seen in all placentas examined and was associated with IUGR in four of seven cases. Maternal uniparental disomy was identified in three cases. Mosaic trisomy 16 detected through amniocentesis is not a benign finding but associated with a high risk of abnormal outcome, most commonly IUGR, CHD, developmental delay, and minor anomalies. The various outcomes may reflect the diversity of mechanisms involved in the resolution of this abnormality. As 80% of these patients were ascertained because of the presence of abnormal levels of MSAFP or MShCG, the increased use of maternal serum screening should bring more such cases to clinical attention. Am. J. Med. Genet. 80:473–480, 1998. © 1998 Wiley-Liss, Inc.     

Prenatal diagnosis policy without routine amniocentesis in pregnancies with a positive family history for neural tube defects

The recurrence risk for neural tube defects in pregnancies of women with a family history of neural tube defects greatly exceeds the general population risk. In these high risk pregnancies, we used a prenatal diagnostic method differing from that usually employed, relying mainly on the results of maternal serum alpha-fetoprotein (MSAFP) and ultrasound examination, without routine amniocentesis. During the 6 years reviewed in this study, this method was applied in 539 pregnancies. Of a total of 20 neural tube defects, 19 were detected using this combination of MSAFP, ultrasound, and selective amniocentesis, and the authors estimate that about 8-10 spontaneous abortions were avoided because only 28 amniocenteses were carried out instead of 539. The risk of recurrence was found to be lower than that experienced earlier.     

Second-trimester maternal serum alpha-fetoprotein levels and the risk of subsequent fetal death.

BACKGROUND. The finding of an elevated level of maternal serum alpha-fetoprotein during the second trimester of pregnancy may indicate that the fetus has died or is about to die. It is uncertain, however, whether the finding is associated with an increased risk of fetal death later in gestation independent of known causes of elevation, such as the presence of neural-tube defects or multiple gestation. METHODS. To address this question, we performed a case-control study of 612 women whose pregnancies ended in fetal death and 2501 women who gave birth to live infants, using reports from California vital statistics for 1987. All the women had signleton pregnancies and alpha-fetoprotein screening in the second trimester. RESULTS. Women with elevated levels of serum alpha-fetoprotein in the second trimester of pregnancy had an increased risk of fetal death, and the risk was increased until term. Women with the highest levels of serum alpha-fetoprotein--greater than or equal to 3.0 times the median value--had a very high risk of fetal death (odds ratio, 10.4; 95 percent confidence interval, 4.9 to 22.0) as compared with women who had normal levels of alpha-fetoprotein. Maternal serum alpha-fetoprotein levels that were 2.0 to 2.9 times the median were also associated with an elevated risk of fetal death (odds ratio, 2.4; 95 percent confidence interval, 1.7 to 3.4). Elevated levels of alpha-fetoprotein were especially likely to be associated with fetal death in cases in which maternal hypertension or placental infarction was also present. CONCLUSIONs. An unexplained elevated level of maternal serum alpha-fetoprotein in the second trimester of pregnancy is associated with an increased risk of subsequent fetal death, up to four to five months after alpha-fetoprotein screening.     

Distress Associated with Prenatal Screening for Fetal Abnormality

A theoretically-based, multivariate approach was used to identify factors associated with emotional distress for pregnant women undergoing maternal serum alpha fetoprotein (MSAFP or AFP) testing, used to detect abnormalities of the fetal brain and spinal cord. Participants were those who received normal results (N = 87). Study results supported the hypothesis that different factors would predict distress before and after testing. Satisfaction with information about testing predicted lower emotional distress early in the testing process; concerns about the child having other medical conditions and low-dispositional optimism predicted distress later. Study findings indicate that even in women who receive normal test results, AFP testing is associated with a modest degree of emotional disturbance which declines, but does not completely abate, after testing.     

Prophylactic Cerclage to Prevent Preterm Birth after Conization: A Cohort Study Using Data from the National Health Insurance Service of Korea

PurposeTo investigate potential differences in the frequency of preterm births (PTB) between pregnancies with or without prophylactic cerclage in women with a history of conization.Materials and MethodsWe identified women who had their first singleton delivery after conization between 2013 and 2018 using records in the National Health Insurance Service of Korea claims database. We only included women who had undergone a health examination and interview within 2 years before delivery. We used timing of maternal serum alpha-fetoprotein (MSAFP) tests to differentiate early (before) from late (after the MSAFP test) cerclage. The frequency of adverse pregnancy outcomes, including PTB, preterm labor and premature rupture of membranes, antibiotics and tocolytics use, cesarean delivery, and number of admissions before delivery, were compared.ResultsA total of 8322 women was included. Compared to the no cerclage group (n=7147), the risks of adverse pregnancy outcomes were higher in the cerclage group (n=1175). After categorizing patients with cerclage into two groups, the risk of PTB was still higher in the early cerclage group than in the no cerclage group after adjusting for baseline factors (4.48%, 30/669 vs. 2.77%, 159/5749, odds ratio 2.42, 95% confidence interval 1.49, 3.92). Other adverse pregnancy outcomes were also more frequent in the early cerclage group than the no cerclage group.ConclusionEarly cerclage performed before MSAFP testing does not prevent PTB in pregnancy with a history of conization, but increases the risk of adverse pregnancy outcomes, including PTB.