9969例孕中期孕妇产前筛查结果分析

目的分析孕中期母体血清hAFP、freeβ-HCG、uE3的变化及产前筛查的应用价值。方法采用时间分辨荧光免疫技术检测孕中期母体血清标志物hAFP、freeβ-HCG、uE3的含量,结合孕妇年龄、孕周、体重等因素用Risk2T软件进行风险评估,根据评估结果,将同孕周高、低风险孕妇的hAFP、freeβ-HCG、uE3含量进行统计分析;同时,建议高风险孕妇进一步确诊。结果低风险母体血清hAFP、uE3含量与孕周呈正相关,freeβ-HCG含量与孕周呈负相关;21-三体高风险母体血清hAFP、uE3含量明显低于低风险母体血清该指标含量,差异有统计学意义（P〈0.01）;而freeβ-HCG含量明显高于低风险时该指标含量,差异有统计学意义（P〈0.01）;18-三体高风险的母体血清hAFP、freeβ-HCG含量均低于低风险时该指标含量,差异有统计学意义（P〈0.01）。9969例孕妇中,筛查出21-三体、18-三体及NTD高风险共288例,筛查阳性率2.9%;107例进行了产前诊断,共确诊19例,确诊率为17.8%,分别为：21-三体6例、18-三体2例,NTD 3例,其他异常儿8例。结论孕中期母体血清3项指标呈规律性变化,检测该指标可发现高风险孕妇;产前筛查结合产前诊断能有效降低出生缺陷率。     

孕中期异常甲胎蛋白与不良妊娠结局的相关性

目的探讨孕中期甲胎蛋白(AFP)与不良妊娠结局的相关性,为妊娠管理提供建议。方法对孕中期14 008例孕妇进行唐氏筛查。研究组:①AFP MoM>2.0孕妇338例。②AFP MoM<0.5孕妇224例。依据AFP MoM值不同分组。对照组:AFP MoM值都在正常范围内的孕妇318例。回顾分析妊娠结局资料。结果①AFP MoM>2.0的孕妇发生出生缺陷(P<0.01)的机会明显比正常孕妇高。②AFP MoM>3.5的孕妇发生出生缺陷(P<0.001)和早产(P<0.05)的机会明显比正常孕妇高。③AFP MoM>5.0的孕妇发生出生缺陷(P<0.001)、早产(P<0.01)和胎儿窘迫(P<0.05)的机会明显比正常孕妇高。④AFP MoM<0.5和<0.25的孕妇均未发现与不良妊娠结局相关。结论异常水平的标志物除了能够提供开放性神经管缺损风险外,还能提供不良妊娠结局的风险信息,而这些信息对产前遗传咨询和妊娠管理是非常重要。     

唐氏综合征孕中期多指标联合筛查方案适用性评估

目的 对孕中期多种产前筛查方案进行比较、评价,为选择较为适宜的方案提供依据.方法 收集2009年在青岛市产前诊断中心知情同意接受产前筛查的单活胎妊娠30 547例,分别检测母血清中二联或三联血清标记物,均用Lifecycle软件评估胎儿罹患唐氏综合征的风险,对二者的检出率和成本效益进行比较、分析;同时收集64例唐氏综合征妊娠的血清标本,采用二联筛查(double test,DT)+2T-Risks软件计算风险(DT-2T),二联筛查+Lifecycle软件计算风险(DT-LC),三联筛查(triple test,TT)+2T-Risks软件计算风险(TT-2T)和三联筛查+ Lifecycle软件计算风险(TT-LC)4种不同的筛查方案对胎儿罹患唐氏综合征的风险进行评估,并对各种不同的筛查方案进行比较、评价.结果 (1)64例唐氏综合征妊娠的血清标本,采用Lifecycle软件进行风险评估,检出率均高于同样指标筛查而采用2T-Risks软件评估风险方案;三联筛查不适宜使用2T-Risks软件;(2)30 547例单活胎妊娠的筛查中,DT-LC方案和TT-LC方案对于唐氏综合征的检出率分别为56.25%和57.14%;每检出1例唐氏综合征的平均费用DT-LC方案明显低于TT-LC方案,为优选方案.结论 孕中期DT-LC方案是一种利于在全国广泛开展的、经济有效的筛查方案.

Abstract：

Objective To provide basis for selecting the suitable method of Down's syndrome biochemical screening in the second trimester pregnancy. Methods A total of 30 547 singleton pregnancies between 14 and 20+6 weeks of pregnancy were collected and analyzed for maternal serum alpha-fetoproteins (AFP) and human chorionic gonadotrophin,free beta subunit (β-HCG) with or without unconjugated estriol (uE3). The screening risks were calculated using the software Lifecycle. The detection rates and the cost of per Down's syndrome detected were calculated and compared. And four different methods were compared in a series of 64 serum samples from Down's syndrome pregnancies. Results (1) Among the 64 affected cases, the detection rate of Down's syndrome was improved no matter in the double test (DT) or in the triple test (TT) if software Lifecycle (LC) was used to evaluate risks. And it was not suitable to evaluate risks with software 2T-Risks in the triple tests. (2) In the cohort of 30 547 singleton pregnancies, the detection rate of Down's syndrome with project DT-LC, which was double test using AFP and free β-HCG together with software Lifecycle, and project TT-LC, which was triple test using AFP, free β-HCG and uE3 together with software Lifecycle, was 56.25% and 57.14%, respectively. The former project was better because it decreased the false positive rate at a lower running cost. Conclusion The DT-LC is an effective screening strategy for second trimester detection of fetal Down's syndrome in mainland China.     

Weight correction of MoM values: which method?

BACKGROUND: Adjusting maternal serum markers for maternal weight is considered to be a standard practice when screening for pregnancies associated with Down's syndrome. The choice of model for taking maternal weight into account is, however, rarely explicitly evaluated. METHOD: The relationship between the maternal serum markers alphafetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3), determined with the Beckman Coulter access reagents and maternal weight was investigated in a cohort of 752 Belgian women being screened for pregnancy associated with Down's syndrome. Two different models (the log-linear equation and the linear-reciprocal equation) were used to determine the relationship between the serum markers and maternal weight. RESULTS: A significant relationship between log(10) multiples of median (MoM) values and weight (kg) was obtained for all markers, and the log-linear model had higher coefficients of determination (r(2)) when compared with the linear-reciprocal model. Weight correction with either method achieved the optimum effect that the correction factor for a woman with a population median weight of 65.5 kg was not significantly different from 1. Simulated weight-corrected MoM values with the two approaches were compared and variation was estimated. The mean difference between the weight-corrected MoM values calculated by the two methods was 7.8% (SD 4.3%) for AFP, 14.0% (4.4%) for HCG and 5.9% (3.2%) for uE3. This resulted in a difference in risk estimate of 1.66-5.34% for Down's syndrome owing to weight correction algorithm differences in women of median weight. CONCLUSION: The log-linear weight correction approach was shown to be marginally more effective by a goodness-of-fit analysis. Differences in weight-corrected MoM values estimated with the two approaches are highly significant (p<0.0001, Wilcoxon's paired sample test), but the effect on risk calculation was not significant. It was observed that the changes in risk became significant the more the MoM correction factors deviated from 1.     

Analysis of triple test results in 27 cases of twin pregnancies

The study comprises 889 pregnant women between 14 and 21 weeks of gestation. The control group consisted of 862 pregnant women with unburdened obstetric anamnesis with an uneventful singleton pregnancy. The examined group consisted of 27 pregnant women with uncomplicated twin pregnancy. In the sera of pregnant women AFP (Microparticle Enzyme Immunoassay AxSYM Abbott), total beta-hCG (Microparticle Enzyme Immunoassay AxSYM Abbott) and unconjugated estriol (Radioimmunoassay Amerlex-M. 2T Johnson & Johnson Ortho Clinical Diagnostics Ltd.) were determined. The risk of fetal trisomy 21 was calculated with the use of PRISCA 3.0 software, which corrected the MoM values for twin pregnancy. Ulm Index was also calculated. In the majority of twin pregnancies increased concentrations of AFP, total beta-hCG and uE3 in the range over 1.0 MoM was noted. In the group of women below 35 years of age with singleton pregnancies using PRISCA 3.0 software it approximated to 95%. For women older than 35 optimum index for fetal trisomy 21 risk calculation was Ulm Index with the specificity 93.8%. The specificity of AFP determination in the detection of fetal open NTD in singleton pregnancy was 99%. In the group of women with twin pregnancy the obtained specificity of 77.8% for PRISCA 3.0 software is low, a more advantageous way to calculate the risk of fetal trisomy 21 is Ulm Index with the specificity of 85.2%. The specificity of AFP determination as a screening for fetal open NTD in twin pregnancy was 96.3%.     

Predictive value of the triple screening test for the phenotype of Down syndrome.

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in the second trimester ("triple" test) and combined with maternal age to evaluate risk for fetal Down syndrome. Triple test results and clinical findings were retrospectively reviewed for 30 newborns with Down syndrome to determine whether analyte values or second trimester risks for Down syndrome were more extreme in affected pregnancies where cardiac or other severe congenital malformations were present compared to those cases where major anatomical abnormalities were absent. Mean MS-AFP, uE3, maternal age, and second trimester Down syndrome risk were all similar in the two groups of pregnancies. However, hCG concentrations did appear to be higher in the group of Down syndrome pregnancies with anatomical anomalies (mean 1.74 MoM versus 1.19 MoM) (P<0.05). Overall, there was no significant difference in the incidence of major anomalies in patients with screen-positive test results versus those cases that were not identified by the triple test. Prenatal counseling should therefore reflect the general expectations of the Down syndrome phenotype that have been established from live-born infants with this disorder.     

Triple marker screening for fetal chromosomal abnormalities in Korean women of advanced maternal age

The purpose of this article is to assess the value of maternal serum triple marker screening of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) for the prenatal diagnosis of fetal chromosomal abnormalities in Korean women of advanced maternal age. Maternal sera were collected from 458 pregnant Korean women aged 35 between 15 and 20 weeks gestation before amniocentesis. A patient- specific second trimester risk for fetal Down's syndrome was calculated using the median values for AFP, hCG, uE3 and maternal age. Twelve fetal chromosomal abnormalities were identified. These included six cases of trisomy 21, one case of 46,XY/47,XY,+21, two cases of trisomy 18, one case of trisomy 13, and two cases of 45, X. A cutoff level of 1:200 detected 85.7% (6/7) of the cases of Down's syndrome and 20% (1/5) of the other aneuploidies, with a 27.3% false positive rate. However, a cutoff level of 1:270 did not result in any gains in detecting Down's syndrome or other aneuploidies at the expense of a false positive rate of 34.3%. Second trimester triple marker testing is an effective screening tool for detecting fetal Down's syndrome in Korean women > or = 35 years old. However, it is not an effective screening tool for non-Down's chromosomal abnormalities.     

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.     

Predictive value of the triple screening test for the phenotype of Down syndrome

Maternal serum alpha-fetoprotein (MS-AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in the second trimester (“triple” test) and combined with maternal age to evaluate risk for fetal Down syndrome. Triple test results and clinical findings were retrospectively reviewed for 30 newborns with Down syndrome to determine whether analyte values or second trimester risks for Down syndrome were more extreme in affected pregnancies where cardiac or other severe congenital malformations were present compared to those cases where major anatomical abnormalities were absent. Mean MS-AFP, uE3, maternal age, and second trimester Down syndrome risk were all similar in the two groups of pregnancies. However, hCG concentrations did appear to be higher in the group of Down syndrome pregnancies with anatomical anomalies (mean 1.74 MoM versus 1.19 MoM) (P < 0.05). Overall, there was no significant difference in the incidence of major anomalies in patients with screen-positive test results versus those cases that were not identified by the triple test. Prenatal counseling should therefore reflect the general expectations of the Down syndrome phenotype that have been established from live-born infants with this disorder. Am. J. Med. Genet. 85:123–126, 1999. © 1999 Wiley-Liss, Inc.     

Maternal serum hCG and alpha-fetoprotein levels in pregnancies conceived after IVF or ICSI with fresh and frozen-thawed embryos

BACKGROUND: Studies have shown that levels of serum markers of Down's syndrome were altered in pregnancies conceived after IVF, though the reason for this remains unknown. METHODS: Second-trimester maternal serum levels of hCG and alpha-fetoprotein (AFP) in pregnancies conceived with fresh and frozen-thawed embryos after assisted reproduction were compared with those conceived spontaneously. RESULTS: There were 203 pregnancies with fresh embryo transfers (130 IVF cases, 73 ICSI cases) and 98 pregnancies with frozen-thawed embryo transfers (61 IVF cases, 37 ICSI cases). The controls consisted of 17 145 spontaneous pregnancies. The median hCG multiples of the median (MoM) was significantly increased to 1.24 in 98 pregnancies conceived after frozen embryo transfer. This elevation was observed only in the IVF-frozen embryo transfer subgroup (P < 0.001), but not in the ICSI-frozen embryo transfer subgroup. The median AFP MoM for 203 pregnancies after fresh embryo transfer was 0.90. Among the subgroups, the median AFP MoM was significantly reduced to 0.90 and 0.86 in IVF-embryo transfer (P = 0.04) and ICSI-embryo transfer (P = 0.001) pregnancies respectively, and significantly raised to 1.20 in the IVF-frozen embryo transfer subgroup. CONCLUSIONS: The degree of alterations in maternal serum hCG and AFP levels varied between fresh and frozen-thawed embryos, and also between the mode of fertilization. Pregnancies resulting from ICSI or frozen embryo transfer should be regarded as distinct entities from those of IVF-embryo transfer.     

Comparison of triple serum screening and pregnancy outcome in oocyte donation versus IVF pregnancies

The current study compared triple serum screening results and outcomes in 37 oocyte donation (OD) and 46 self oocyte IVF-conceived singletons of similarly aged women (28.8 +/- 4.4 years and 30.7 +/- 4.5 years respectively). Both groups were followed from their embryo transfer and throughout pregnancy. Although the daily pattern of first-trimester serum beta-human chorionic gonadotrophin (HCG) was similar in both groups, higher mid-gestation HCG serum concentrations were found, i.e. 1.38 and 1.32 multiples of the median (median MoM) for IVF and OD respectively, in comparison with 0.99 median MoM from the same reference laboratory. Only the OD group had significantly increased alpha fetoprotein (AFP) concentrations (1.45 median MoM) (P = 0.002) compared with the reference laboratory. A total of 11% of the IVF and 13% of the OD women were found to be screen positive. In neither group were chromosomal abnormalities detected and no fetal or neonatal deaths were recorded. Seven (15%) of the OD and seven (19%) of the IVF women had an adverse obstetric outcome. Of those cases, six IVF and four OD women had serum HCG > or = 1.2 MoM and five OD women had AFP >1.2 MoM. Therefore, in those pregnancies the high serum HCG concentrations may alert for adverse obstetric outcome rather than indicating a high risk for Down's syndrome fetuses.     

Abnormal maternal serum levels of human chorionic gonadotropin free subunits in trisomy 18

We have measured maternal serum levels of free alpha and beta subunits of human chorionic gonadotropin between 8 and 12 weeks of gestation in 704 women at increased risk for trisomy. This group was studied because of advanced maternal age or a previous birth with chromosomal abnormality. All sera had been collected prior to chorion villus biopsy for prenatal diagnosis. Serum levels of free alpha and beta hCG were determined by specific monoclonal antibody-based immunoradiometric assays. Analysis of chorionic tissue showed that in 38 of 704 (5.4%) pregnancies the fetus had a chromosome abnormality. There were 8 fetuses with trisomy 18 (1.1%) and 9 (1.3%) with trisomy 21. In all pregnancies carrying a trisomy 18 fetus, we observed either high levels of free alpha hCG or low levels of free beta hCG or both. More importantly, the calculated ratio of free beta hCG/alpha hCG was less than 0.25 multiples of the median (MoM) in 6 of 8 (75%) trisomy 18 cases. Only 21 of 666 mothers (3.2%) carrying a normal fetus had a ratio less than 0.25 MoM (P less than 0.0001). There was no difference between this ratio in trisomy 21 and normal pregnancy. Thus, when adjusted for gestational age, a low free beta hCG/alpha hCG ratio in maternal serum indicates a pregnancy at high risk [RR = 72 (95% CI 32, 162)] for trisomy 18.     

Medians for second-trimester maternal serum markers: geographical differences and variation caused by median multiples-of-median equations

OBJECTIVES: To establish gestational age-specific mid-trimester normal medians for the prenatal serum markers alpha fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3) for a Belgian population by using the Beckman Coulter Access chemiluminiscent immunoassays; to compare these data with data obtained from other geographical regions; to propose regression coefficients for regressed medians and analyse variation induced by different regression equations; to evaluate the effect of formulas used for gestation correction on estimating risk in Down's syndrome. DESIGN: Data derived from 862 fresh serum samples from women being screened for Down's syndrome pregnancy, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Regressed medians were calculated by using a first-degree logarithmic-linear fit of the raw data. Multiples-of-median (MoM) values estimated by using a simple logarithmic-linear equation were compared with those calculated with higher-degree polynomials chosen with a goodness-of-fit analysis. Model-specific variation was estimated and the effect on risk for Down's syndrome was evaluated. RESULTS: Regressed medians (Y) for Access serum markers AFP (IU/ml), HCG (IU/ml) and uE3 (nmol/l) for a Belgian population can be estimated with the equation Y = 10((A+BX)) with X = decimal weeks. The best fit was obtained with a third-degree and a second-degree polynomial for AFP and uE3, respectively. Differences between the medians and among the slopes of the geographical populations were found to be significant (analysis of covariance, p<0.001). CONCLUSIONS: Belgian marker medians versus gestational time are found to show a pattern that is similar to that in the literature. The log-linear equation is observed to give a good fit and can be suggested as a tool for calculating median MoM values for Belgian laboratories that use Access biochemical prenatal markers.     

兰州地区孕妇孕中期产前筛查结果回顾性分析

目的通过检测孕妇血清中AFP,Free-βhOG和uE3的浓度,对孕中期胎儿患DS、ES和NTD的风险进行评估。方法运用时间分辨荧光法定量测定孕妇血清中AFP,Free-βhC6和uE,的浓度,采用“Life cycle 3．2”软件计算风险。结果9430例孕妇中高龄共289例,占总筛查人数的3．06％,其中DS、BS和NTD的阳性筛查率分别为5．4％（1／19）、0．21％（1／476）和O．32％（1／313）。确诊阳性病例19例,其中高龄lO例。结论孕中期母血清三联产前筛查是检测胎儿染色体异常的有效途径,对降低出生缺陷,提高人口素质有重要意义。     

孕中期高溶度Free-β-hCG预测不良妊娠结局的价值

目的探讨孕中期母血清Free-β-hCG升高与不良妊娠结局的相关性。方法采用时间分辨免疫荧光分析法对孕中期7121例孕妇进行唐氏筛查,427例孕妇血清Free-β-hCG MoM≥2.5（其中MoM≥3.5,184例;MoM≥5.0,58例）。收集妊娠结局资料进行分析,Free-β-hCG MoM在中位数周围的孕妇为对照组。结果Free-β-hCG MoM≥5.0,≥3.5,≥2.5三组中,胎膜早破均高于对照组（P〈0.05）;出生后需进入新生儿监护中心（NICU）特别护理的婴儿均高于对照组（P〈0.05）,具有统计学意义。MoM≥5.0组中,出生婴儿出生体重低于对照组（P=0.046）,具有统计学意义。结论Free-β-hCG升高的孕妇处于不良妊娠结局的高风险中,对孕中期Free-β-hCG MoM≥2.5孕妇增加监护的有必要的。     

Maternal serum hCG and SP1 in pregnancies with fetal aneuploidy

In a retrospective study, maternal serum levels of chorionic gonadotropin (hCG) and pregnancy specific beta 1-glycoprotein (SP1) from 63 pregnancies with aneuploid fetuses were compared to the levels observed in pregnancies with a chromosomally normal fetus. Thirty-eight percent of the abnormal pregnancies had elevated levels (greater than 2.0 multiples of the normal median [MoM]) of hCG and 14% had depressed levels (less than 0.25 MoM). With a false-positive rate of 5%, 44% of the 42 fetuses with trisomy 21 would have been detected by elevated hCG levels. With the same false-positive rate, only 21% had elevated SP1 levels. hCG was significantly depressed in 12 pregnancies affected by fetal trisomy 18.     

Prenatal maternal blood screening for the detection of fetal chromosomal abnormalities: clinical importance of the rate of false positives

Maternal serum screening to identify fetal aneuploidies is now routinely offered during the second trimester of pregnancy in developed countries. The purpose of this prospective study was to assess the value of maternal serum screening between 15 and 20 weeks of gestation to detect fetal aneuploidies and to determine the false positive rate (FPR). Blood samples were collected from 1,062 pregnant women between 15 and 20 weeks of gestation. Samples were assayed for alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (beta-hCG) and unconjugated estriol (uE3). Medians were established at each week from 200 normal, singleton pregnancies. Second trimester risk was calculated using the maternal age and different combinations of AFP, beta-hCG and uE3. Screening results calculated by likelihood ratio to be equal to or greater than 1:270 were considered positive. If the gestational age was confirmed by ultrasonography, genetic counselling and amniocentesis were offered. Ten fetal chromosomal abnormalities were detected with maternal serum screening. Sample's size does not allow a correct detection rate estimation, but false positive rate (FPR) was found to be 6.5%. This FPR has a clinical application. At a cut-off of 1:270, second trimester screening best results were obtained using a combination of all three biochemical markers. These results confirm the efficacy of maternal serum screening for fetal chromosomal abnormalities with a low FPR. The measurement of AFP, beta-hCG and uE3 is an effective prenatal screening test.     

Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome

BACKGROUND: The aim of this study was to compare the maternal mid-trimester free beta-HCG and alpha-fetoprotein (AFP) levels in pregnancies conceived by assisted reproduction technology and spontaneous pregnancies in Down's syndrome screening. The influence of the number of embryos transferred and the amount of gonadotrophins used on the marker levels was also evaluated. METHODS: The study population consisted of 58 IVF, 32 ICSI and 26 frozen embryo transfer (FET) singleton pregnancies. The levels of beta-HCG and AFP were compared with the control group of 6548 singleton spontaneous pregnancies. RESULTS: The false positive rate (FPR) in the Down's syndrome screening was 19% overall in assisted reproductive technology pregnancies, being highest (30.8%) in the FET group. The free beta-HCG multiples of the median (MoM) values were statistically significantly elevated only in the FET group (1.33 MoM; P = 0.012). A positive correlation between the number of embryos transferred and the marker levels was observed in the IVF group. No correlation was found between the amount of gonadotrophin medication used and the marker levels. CONCLUSIONS: The present data confirm that the overall FPR in the serum screening for Down's syndrome in assisted reproduction pregnancies is high, resulting in unnecessary invasive procedures.     

Maternal serum markers levels in consecutive pregnancies: A possible genetic predisposition to abnormal levels

The study comprised 2,361 women, each with two consecutive normal uncomplicated pregnancies screened at 15–20 weeks gestation for maternal serum alpha-fetoprotein levels (AFP). In 1,816 of these women, maternal serum human chorionic gonadotropin (hCG) levels were tested as well. The proportion of women who had a second high AFP level (≥2.0 MOM) in their subsequent pregnancy was 6.5-fold higher as compared with the proportion of women who had normal levels of AFP in their first tested pregnancy. The relative chance of having a second positive result of a low level of AFP (AFP ≤0.5 MOM) in subsequent pregnancies was 3.8-fold higher. The relative chances of having a second positive result of high or low levels of hCG were 3.9- and 2.2-fold higher, respectively. It is concluded that there is a predisposition for abnormal levels of serum markers that is influenced by genetic and/or environmental factors. Therefore it is suggested that the individual's risk of having a Down syndrome baby, or other adverse pregnancy outcome that is derived from the serum markers' levels, should be adjusted taking into account unexplained high or low levels in previous pregnancies. A screening policy is suggested which is designed to yield a lower false-positive rate without affecting the detection rate of abnormal pregnancies. More data are needed before an accurate adjustment based on previous results can be made. © 1996 Wiley-Liss, Inc.     

Second trimester maternal serum pregnancy specific beta-1 glycoprotein (SP-1) levels in normal and Down syndrome pregnancies

Maternal serum pregnancy specific beta-1 glycoprotein (SP-1) levels in the second trimester may be predictive of Down syndrome (DS). An enzyme immunoassay was used to measure SP-1 sera from 46 DS pregnancies and 117 normal control women matched for maternal age, gestational age, and length of storage. In the normal control samples, there were slight correlations between the SP-1 concentration and maternal age. The maternal serum SP-1 levels increased with each week of gestation from 15 to 20 weeks. All but one of the DS sera had SP-1 levels greater than the normal median. Using a cutoff of 2.8 multiples of the median (MoM), 15.2% of the DS pregnancies were detected with a false-positive rate of 4.3%. A combinational logistic regression analysis of maternal age and pregnancy related serum proteins will detect additional DS pregnancies and decrease the false-positive rate. The combination of maternal age and SP-1 detected 33 (71.7%) of Down syndrome pregnancies. The addition of maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels allowed for the detection of 36 (78.3%) of the DS pregnancies with a decrease in the false-positive rate to 3.4%. The measurement of other serum constituents in conjunction with AFP appears to be a valuable addition to current screening programs, as this can increase the proportion of DS cases detected prenatally.