Maternal Serum Α-fetoprotein Research Articles

Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers

Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3- to 4-fold, in open spina bifida. We assessed whether combined screening using BPD, AFP, and other serum markers at 11-13 weeks would increase detection. Maternal AFP levels were measured on serum stored at 11-13 weeks in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median (MoM) for gestational age. All samples had been measured for free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published. The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P < .01, 1 tail). The median free β-hCG was significantly reduced to 0.820 MoM (P < .02), but the median PAPP-A was similar in cases and controls. Modeling predicted the following: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; and a combined test with BPD, AFP, and free β-hCG detects 58% for 5% or 70% for 10%. Combining AFP and BPD with free β-hCG as part of first-trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.

Maternal serum placental growth factor and α‐fetoprotein testing in first trimester screening for Down syndrome

The aim of this research was to evaluate the addition of first trimester maternal serum placental growth factor (PlGF) and α-fetoprotein (AFP) to the combined test for Down syndrome and a serum only protocol of PlGF, AFP, free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Samples were from 92 Down syndrome cases with 552 matched controls. All women had a combined test at 11-14 weeks gestation. PlGF and AFP were measured and expressed in multiples of the gestation-specific median (MoM), adjusting for maternal weight and smoking status. Multivariate Gaussian modeling was used to predict detection and false-positive rates. The median PlGF level in the cases was 0.694 MoM and controls 1.000 MoM (p = <0.0001). The corresponding values for AFP were 0.764 MoM and 0.990 MoM (p < 0.0001). Statistical modeling predicted that for a given false-positive rate, the addition of PlGF to the combined test increases the detection rate by 4-7%. For a given detection rate, the false-positive rate could be almost halved. When both PlGF and AFP are used, the detection rate increase is 5-8%. A serum only protocol had a predicted a detection rate of 71% for a false-positive rate of 5%. Results suggest a substantial benefit of adding PlGF to the combined test.

Second trimester maternal serum markers and a predictive model for predicting fetal hemoglobin Bart’s disease

Objective: To compare the levels of maternal serum α-fetoprotein (AFP), unconjugated estriol (uE3) and free β-human chorionic gonadotropin (free β-hCG) between pregnancies with fetal Hb Bart’s disease and unaffected pregnancies. Methods: 148 pregnancies at risk of fetal Hb Bart’s disease scheduled for cordocentesis at 18 to 22 weeks were prospectively recruited into the study. AFP, uE3 and free β-hCG concentrations were measured before cordocentesis and the final fetal diagnosis of Hb Bart’s disease was based on fetal Hb typing using high-performance liquid chromatography. Results: AFP and free β-hCG were significantly higher whereas uE3 was lower in women with fetal Hb Bart’s disease than those with unaffected fetuses (1.94 MoM, 1.38 MoM and 0.81 MoM respectively). Hb Bart’s predictive model; probability = 1/1+e−[2.876 + 1.333(AFP) − 6.310(uE3)], effectively predicted fetal Hb Bart’s disease (AUC ROC 0.91, 95% CI 0.84–0.97) with 61.5% sensitivity and 98.1% specificity using a cut-off probability at greater than 0.5. Conclusions: In triple test, serum AFP and hCG levels are significantly higher while serum uE3 is significantly lower in pregnancies with fetal Hb Bart’s disease. Hb Bart’s predictive model included AFP and uE3 is relatively effective and may be helpful in Hb Bart’s prenatal screening.

Elevated midtrimester α-fetoprotein and delivery markers of inflammation in a preterm population

Objective: Determine whether elevated second trimester maternal serum α-fetoprotein (AFP) is associated with clinical and histopathologic markers of inflammation at preterm delivery. Methods: 105 women <32 weeks’ gestation were included. AFP levels were dichotomized at 2.0 multiples of the median (MoM). Rates of neonatal morbidities, clinical chorioamnionitis, cord blood IL-6 level, and placental inflammatory findings were compared. Results: Thirteen (12.4%) had elevated AFP. Fewer women with AFP ≥2 MoM had histologic placental or membrane rupture site inflammation, funisitis, or placental culture positive for Mycoplasma and Ureaplasma species, compared to those with normal AFP. Neonatal death was increased in the elevated AFP group (23.1% vs. 2.27%, RR 10.6). Elevated AFP was associated with a nonsignificant increase in indicated birth (54% vs. 35%; p = 0.225). Virtually all inflammatory findings were confined to the spontaneous delivery group. Conclusion: Elevated midtrimester AFP conveyed significant risk of neonatal death, but was negatively associated with clinical or histopathologic inflammation in preterm infants.

Abnormal second-trimester serum analytes are more predictive of preterm preeclampsia

We sought to determine the association of abnormal second-trimester serum analytes with early preterm preeclampsia. We conducted a retrospective study of 7767 subjects undergoing second-trimester serum aneuploidy screening. Values of maternal serum α-fetoprotein (AFP), β-human chorionic gonadotropin (hCG), and inhibin (INH) were calculated as multiples of the median (MoM) and evaluated by gestational age at delivery and occurrence of preeclampsia. Of 459 (6.5%) cases of preeclampsia, 65 (14%) delivered <34 weeks and 394 (86%) delivered >34 weeks. Elevated AFP, hCG, and INH >2 MoM were associated with preeclampsia, and the odds ratio was higher for the development of preeclampsia <34 weeks than >34 weeks (odds ratio, 8.04 vs 2.91 for AFP, 3.6 vs 2 for hCG, and 4.17 vs 3.08 for INH, P < .001 for all). The higher the MoM for each analyte the greater the likelihood of preeclampsia. Elevated AFP, hCG, and INH levels >2 MoM are associated with developing early preeclampsia, and the more elevated they are, the higher the likelihood.

Risk of bronchopulmonary dysplasia by second-trimester maternal serum levels of α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol

Although maternal serum alpha-fetoprotein (AFP), human chorionic gonandotrophin (hCG), and estriol play important roles in immunomodulation and immunoregulation during pregnancy, their relationship to the development of bronchopulmonary dysplasia (BPD) in young infants is unknown despite BPD being associated with pre- and postnatal inflammatory factors. The objective of this population-based study was to examine whether second trimester levels of AFP, hCG, and unconjugated estriol (uE3) were associated with an increased risk of BPD. We found that these serum biomarkers were associated with an increased risk of BPD. Risks were especially high when AFP and/or hCG levels were above the 95th percentile and/or when uE3 levels were below the 5th percentile (relative risks (RRs) 3.1 to 6.7). Risks increased substantially when two or more biomarker risks were present (RRs 9.9 to 75.9). Data suggested that pregnancies which had a biomarker risk and yielded an offspring with BPD were more likely to have other factors present that suggested early intrauterine fetal adaptation to a stress including maternal hypertension and asymmetric growth restriction.

Prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3) presenting as apparent isochromosome 18q in a fetus with holoprosencephaly

Objective To present prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). Materials, Methods, and Results A 32-year-old woman was referred for genetic counseling of prenatally detected isochromosome 18q [i(18q)]. She had undergone amniocentesis at 19 gestational weeks because of a trisomy 18 risk of 1/39 derived from abnormally low levels of maternal serum unconjugated estriol, inhibin A, α-fetoprotein, and total β-human chorionic gonadotropin. Amniocentesis revealed a karyotype of 46,XX,i(18)(q10). Parental karyotypes were normal. Prenatal ultrasound showed alobar holoprosencephaly. Repeated amniocentesis was requested and performed at 21 gestational weeks. Array-comparative genomic hybridization analyses revealed a 14-Mb deletion of 18p11.32-p11.21, a 37.8-Mb duplication of 18q12.1-q22.1, and a 6.9-Mb duplication of 18q22.3-q23. Metaphase fluorescence in situ hybridization study showed the absence of an 18q12.1-specific probe signal in one arm and the absence of an 18q22.2-specific probe signal in the other arm of the derivative chromosome. Quantitative fluorescent polymerase chain reaction analysis determined a paternal origin of the derivative chromosome. The cytogenetic result was 46,XX,der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). The fetus postnatally manifested cebocephaly. Conclusion Concomitant monosomy 18p and trisomy 18q can be associated with holoprosencephaly and abnormal maternal serum screening results. Array-comparative genomic hybridization, fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction are useful in genetic counseling of prenatally detected isochromosomes by providing information on the origin and genetic components of the isochromosome.

Maternal Serum α-Fetoprotein at 11–13 Weeks’ Gestation in Spontaneous Early Preterm Delivery

Objective: To examine the potential value of maternal serum level of α-fetoprotein (AFP) in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery. Methods: Maternal serum concentration of AFP at 11–13 weeks’ gestation was measured in a case-control study of singleton pregnancies delivering phenotypically normal neonates, including 33 cases with spontaneous delivery before 34 weeks and 99 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum AFP in the two outcome groups was compared and the bivariate gaussian distributions were simulated in a previously described screened population of 33,370 pregnancies to estimate the performance of screening for early delivery by a combination of maternal characteristics and obstetric history with serum AFP. Results: In the preterm delivery group compared to the term delivery group, the median serum AFP MoM was higher (1.33 vs. 0.97, p = 0.006). The estimated detection rate of preterm delivery, at a false-positive rate of 10%, from maternal characteristics and obstetric history was 27.5% and this increased to 36.0% with the addition of serum AFP. Conclusions: Measurement of serum AFP at 11–13 weeks improves the prediction of early preterm delivery provided by maternal characteristics and obstetric history.

Clinical features of hepatocellular carcinoma during pregnancy

Objective To explore the clinical features of hepatocellular carcinoma (HCC) during pregnancy. Methods Clinical data of 4 patients with HCC in pregnancy were retrospectively analyzed.Results All 4 patients were positive for hepatitis B surface antigen. A marked increase in maternal serum a-fetoprotein (AFP) was found in 3 patients (310.1-5630.0 ng/ml ). Three patients were diagnosed at their advanced stages and died of disease in the 4th, 6th and 7th months, respectively. One patient diagnosed as having early HCC underwent curative surgery and has been without recurrence for 26 months. Conclusion The overall survival of patients with HCC in pregnancy is grim because most patients are diagnosed in the advanced stage. Surveillance with AFP and ultrasonography should be recommended for pregnant woman for the detection of early HCC, especially in hepatitis B virus carriers from high endemic areas, to improve patient survival. Key words: Carcinoma hepatocellular; Pregnancy; α-fetoprotein

Role of the vascular endothelial growth factor in the inverse relationship between increased nuchal translucency thickness and fetomaternal transfusion

To elucidate the possible etiological role of the vascular endothelial growth factor (VEGF) in the inverse correlation between nuchal translucency (NT) thickness and fetomaternal transfusion (FMT). The level of FMT was determined prospectively in 80 viable, singleton pregnancies in which 10-14-week ultrasonographic scanning, NT thickness measurement; chorionic villus sampling (CVS) for fetal karyotyping and VEGF concentration determination were performed. The grouping procedures were based either on NT thickness (<2 MoM in Group I, and ≥2 MoM in Group II), or on karyotype (euploid in Group A, and aneuploid in Group B). The level of FMT was determined via maternal serum α-fetoprotein levels before and after CVS. The FMT and the VEGF concentration of the chorionic tissue were analysed in comparisons between Groups I and II, and between Groups "A" and "B". The mean level of FMT after CVS was 72.5±21.3 μL and 19.28±5.4 μL in Groups I (n=44) and II (n=36), respectively (P<0.02). The VEGF concentration of the chorionic tissue in Groups I and II was 40.6±16.7 pg/mg protein and 21.1±6.3 pg/mg protein, respectively (P=0.28). The mean level of FMT was 57.9±15.0 μL and 8.1±3.9 μL in Groups A and B, respectively (P<0.003). The VEGF concentration of the chorionic tissue in Groups A and B was 25.9±10.7 pg/mg protein and 21.3±11.3 pg/mg protein, respectively (P=0.77). No difference exists in the VEGF concentration in the aspirated chorionic tissue between Groups I and II and between Groups A and B. A higher level of FMT was observed among the aneuploid pregnancies after CVS than among the euploid cases. Chorionic VEGF does not influence the inverse relationship between the pre-CVS NT thickness and FMT.

The association between preeclampsia and placental disruption induced by chorionic villous sampling

The objectives of this study were (1) to evaluate if the elevation of maternal serum alpha-feto protein (MSAFP) and pregnancy-associated placental protein-A (PAPP-A) in the maternal blood after chorionic villous sampling (CVS) is associated with a higher preeclampsia (PE) rate and (2) to verify the clinical utility of the analytes elevation for predicting PE. A prospective study on 106 subjects who underwent CVS was performed. At the time of CVS, two blood samples were obtained for MSAFP and PAPP-A dosage, the first just before the procedure, and the second one 30 min after the procedure. Cases with abnormal karyotype, major anomalies or preterm delivery were subsequently excluded. The ratio between the two samples was calculated as Sigma (MSAFP or PAPP-A post-CVS/MSAFP or PAPP-A pre-CVS) and it was related to subsequent occurrence of PE. The rate of PE was 5.7% (6/106). Both MSAFP and PAPP-A levels were higher after than before CVS (median ratio = 8.33 and 1.08, respectively). Cases developing PE had significantly higher MSAFP ratio (11.6 vs 7.4, p-value = 0.04) and PAPP-A ratio (1.13 vs 1.08, p-value = 0.009) than those who did not develop PE. Receiver operating characteristic curve analysis showed that PAPP-A ratio was a better predictor of subsequent PE than MSAFP ratio: at a fixed false positive rate of 10%, the detection rates for MSAFP and PAPP-A ratios were 33 and 50%, respectively. The elevation of MSAFP and PAPP-A observed with CVS is associated with increased risk of subsequent PE. The ability of such increases to predict PE appears to be modest.

Comparison of second-trimester maternal serum free-β-human chorionic gonadotropin and α-fetoprotein between normal singleton and twin pregnancies: a population-based study

Background The second-trimester maternal serum screening in twin pregnancy is still controversial, as the serum marker levels in twins are not as clear as those in singletons. This study aimed to evaluate the relationship between the levels of the second-trimester maternal serum free β-human chorionic gonadotropin (free β-HCG) and α-fetoprotein (AFP) in normal twin and singleton pregnancies and to estimate feasible analysis methods for utilizing these markers in second trimester screening for twin pregnancy. Methods On the basis of a prospective population-based study of second-trimester maternal serum screening, the concentrations of maternal serum AFP and free β-HCG of 195 normal twin pregnancy and 26 512 singleton controls at gestational weeks 15 to 20 were measured by time-resolved fluoroimmunoassay in one laboratory. The levels of markers were compared between the twins and singletons using weight-correction and gestational age-specific model. Results According to the research protocol, 95 communities were randomly sampled, which covered the whole Jiangsu province, the east of China. A total of 26 803 pregnant women (98%), from the target population accepted prenatal screening for maternal serum AFP, β-HCG detection, and all babies were followed up for at least six months. There were 197 (0.73%) twin pregnancies, of which one case had fetal trisomy 18, and one case with fetal anencephaly. The others were normal twin pregnancy. From a total enrollment of 26 803 women participants, 26 512 women with normal singleton pregnancies were selected as the model controls. The other 291 pregnancies, including trisomy 21, neural tube defect (NTD), trisomy 18, and other fetal abnormalities, were excluded. No significant differences were found in the medians of gestational age-specific maternal serum free β-hCG and AFP in normal twin pregnancy comparing with twice those in model controls with the exception of the medians for free β-hCG during the 16th gestational week (P=0.012). Conclusion The weight-correction and gestational age-specific levels of Chinese Han population maternal serum free β-hCG and AFP in normal twins were twice the levels as those in the singleton controls during the 17-19 gestational weeks.

From nuchal translucency to intracranial translucency: towards the early detection of spina bifida

It is now clear that the vast majority of major fetal abnormalities can be diagnosed prenatally by ultrasound, that most of these abnormalities can be detected in the first trimester of pregnancy and that women want firsttrimester rather than later diagnosis. It is also clear that effective diagnosis of fetal abnormalities often necessitates the identification of easily recognizable markers which direct the attention of the sonographer to the specific abnormality. Good examples of such markers are the scalloping of the frontal bones (the ‘lemon’ sign) and caudal displacement of the cerebellum (the ‘banana’ sign), observed in the second trimester in most fetuses with open spina bifida, and increased nuchal translucency thickness (NT) which identifies in the first trimester the majority of fetuses with major aneuploidies, lethal skeletal dysplasias and a high proportion of major cardiac defects. It is now widely accepted that increased NT at 11–13 weeks is the single most effective marker of trisomy 21 and all other major aneuploidies. First-trimester screening by a combination of maternal age, fetal NT, nasal bone, Doppler assessment of blood flow in the ductus venosus and across the tricuspid valve together with maternal serum free β-hCG and PAPP-A can identify more than 95% of all major aneuploidies for a screen-positive rate of less than 3%. A major remaining challenge in first-trimester ultrasonography has been the diagnosis of open spina bifida. This challenge, however, may now have been resolved by the realization that open spina bifida can be suspected by an easily detectable marker within the brain in the same mid-sagittal plane of the fetal face as for measurement of NT and assessment of the nasal bone. In normal fetuses the fourth cerebral ventricle presents as an intracranial translucency (IT) parallel to the NT, while in fetuses with open spina bifida there may be absence of the IT 1 .

Prenatal diagnosis and prenatal imaging features of fetal monosomy 1p36

Deletion of the distal end of the short arm of chromosome 1 (1p36) is thought to be a common terminal chromosomal deletion. However, few cases prospectively diagnosed prenatally have been reported. In this case, prenatal ultrasound at 21 weeks of gestation noted the fetus to have mild ventriculomegaly (Vhanterior = 11 mm and Vhposterior = 12 mm) and increased nuchal edema (6 mm). Maternal serum alpha-fetoprotein was normal unlike in a majority of previously described cases. The prenatal ultrasound features were further clarified with fetal MRI. Chromosome analysis following amniocentesis demonstrated a 1p36 deletion, which was confirmed by fluorescence in situ hybridization (FISH). The syndrome associated with 1p36 deletion is well described in infants and is characterized by typical facial features (prominent forehead, straight eyebrows. deep-set eyes, flat nasal bridge and a pointed chin). Other associated features are neurodevelopmental delay, seizures, cardiomyopathy and neurosensory hearing impairment. This case supplements our knowledge of the prenatal features of 1p36. Identification of this deletion by direct chromosomal analysis can be technically difficult and vigilance is required to improve diagnosis. FISH analysis is an important diagnostic adjunct where the diagnosis is suspected following classical G-banding techniques. However, in this chromosomal anomaly there remain few characteristic prenatal signs that are readily diagnosed with prenatal imaging.

Prenatal screening and diagnosis—An introduction

Prenatal screening and diagnosis—An introduction

Angiomyxoma of the Umbilical Cord

Angiomyxoma is a rare tumor of the umbilical cord and is associated with increased perinatal morbidity and mortality. However, the management of these pregnancies in the third trimester is not clearly defined. We present a case of an angiomyxoma of the umbilical cord diagnosed in the second trimester, and highlight the contribution of color Doppler imaging to the early diagnosis of cord anomalies. A 29-year-old, gravida 3, para 1, woman had elevated maternal serum alpha-fetoprotein at 17 weeks of gestation. Ultrasonography at 19 weeks showed a placental mass measuring 2 x 1.5 cm over the insertion site of the umbilical cord. The mass slowly enlarged in size, from 2.72 x 1.09 cm at 21 weeks to 3.9 x 3.9 cm at 33 weeks. Beyond the cord lesion, the development of the fetus was unremarkable. At 38 weeks, a normal female infant was delivered by cesarean section due to previous history of cesarean section. A mass measuring 3.2 cm was found near the insertion site of the umbilical cord to the placenta. Pathologic examination showed proliferation of thin-walled vessels embedded in a myxoid stroma, and the endothelial cells were positive for factor VIII-related antigen. Angiomyxoma is a rare tumor of the umbilical cord and should be considered when using prenatal ultrasound for detection of cystic lesion. Color Doppler imaging can easily and instantly detect perfusion through the umbilical vessels and assess cardiac function. In our case, application of color Doppler imaging for monitoring the relationship between the tumor and the adjacent vessels allowed the fetus to be delivered at term with a favorable outcome.

OP01.18: Combining fetal nuchal fold thickness with second‐trimester biochemistry to screen for trisomy 21

To assess second-trimester screening for trisomy 21 by combining fetal nuchal fold (NF) with maternal serum biochemistry. NF and maternal serum α-fetoprotein (AFP) and free ?-hCG were determined on the same day, at 14–19 weeks of pregnancy. The study population comprised 1811 pregnancies, including 1256 unselected pregnancies undergoing routine risk assessment for trisomy 21 (1999–2002), and 555 high-risk pregnancies prior to amniocentesis (2003–5), 404 of which had positive serum screening tests. Results were expressed in multiples of the gestation-specific median (MoMs). There were 1799 unaffected singleton pregnancies, and their NF distribution approximated to Gaussian over a wide range of values with 5th-95th centile range of 0.63–1.47 MoM. There was a small but statistically significant correlation between NF and log AFP (R = − 0.081, P < 0.001) and an even smaller correlation between NF and free ?-hCG which was not significant (R = 0.035, P = 0.15). Among the 8 trisomy 21 pregnancies, the median NF level was 1.45 MoM (mean 1.74 MoM), a highly statistically significant increase (P < 0.001, one-tail Wilcoxon Rank Sum Test). In pregnancies referred because of a positive serum screening test (389 singleton unaffected, 2 twins, 7 trisomies 21, one monosomy X and 5 other chromosomal anomalies) the use of NF to modify the serum screening risk would reduce the invasive procedures by about a half without a change in the trisomy 21 detection rate. The addition of NF measurement to second-trimester biochemical screening improves screening performance, and could overcome the drawbacks in the implementation of Inhibin-A assay in clinical practice.

Choroid Plexus Cysts

Research shows that there is an association between choroid plexus cysts and aneuploidy. Family physicians treating prenatal patients should understand the management of this sonographic finding. To determine the epidemiology, pathophysiology, and management of prenatal choroid plexus cysts. A 23-year-old patient, gravida 1, para 0, was seen at an inner city Family Medicine health center for prenatal care. A screening ultrasonogram performed at 16 weeks of gestation showed bilateral choroid plexus cysts approximately 5 mm in diameter. The patient declined amniocentesis. Maternal serum triple screen markers (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and estriol) were all normal, as was the level II sonogram at 20 weeks and the fetal echocardiogram at 28 weeks. At birth the baby was found to be normal after a clinical assessment was performed. A review of the literature using MEDLINE with the search strategy of choroid plexus, choroid plexus fetus/fetal, choroid plexus management, choroid plexus treatment, and choroid plexus epidemiology.

The effects of analytical factors on second trimester risk estimations

Objective: Triple test with measured maternal serum α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol combination as a routine procedure for fetal Down's syndrome, trisomy 18 and neural tube defect screening has some intrinsic problems, such as precision. The aim of this study was to evaluate the effect of analytical variation of triple test on prenatal risk estimation. Method: Five different serum pools were prepared and triple test was performed seven times for within run and five times for between run precision determination. Result: Within run and between run, precision values of risk estimations by measuring the same sample for Triple test were calculated to be 7.9–21.4% and 14.1–31.0% for trisomy 21, 13.2–23.7% and 14.2–15.1% for trisomy 18, 47.2 and 42.0 % for neural tube defect, respectively. Conclusion: These results demonstrated that analytical variations have great impact on second trimester risk estimation procedures; therefore, triple test analyses should be carried out in laboratories using strict internal and external quality control programs. Moreover, triple test results should always be interpreted by considering analytical and biological variations.

First trimester maternal serum α-fetoprotein screening for Down syndrome and other aneuploidies

Low maternal serum AFP (MSAFP) values in the first trimester of pregnancy have been associated with an increased risk for chromosome disorders. In our own first trimester chorionic villus sampling (CVS) series, MSAFP determinations were carried out in 1,448 singleton pregnancies. Aneuploidies were detected in 26 of these. The pre-CVS MSAFP values in these pregnancies were compared to those in pregnancies with normal outcome. Statistical analysis did not show a diagnostically useful correlation between low first trimester MSAFP values and aneuploidy in our cohort.