Normal Fetal Karyotype Research Articles

Chromosomal analysis of early fetal losses in relation to transvaginal ultrasonographic detection of fetal heart motion after infertility

Objective: To evaluate the prognostic value of transvaginal ultrasound (TVUS) detection of fetal heart motion (FHM) in view of maternal age and chromosomal analysis of spontaneously aborted fetal tissue. Design: A 3-year retrospective, descriptive study. Setting: Two medical center-based infertility-care facilities. Patient(s): 336 pregnancies were initiated by intrauterine insemination or embryo transfer for women of reproductive age who were seeking infertility treatment. Intervention(s): None. Main Outcome Measure(s): βhCG levels measured >40 mIU/mL at 4–5 weeks' gestation and were followed by an initial TVUS at 5–8 weeks. Of these pregnancies, 52 ended in a first trimester loss. Twenty were defined by failure to detect FHM by 7 weeks' gestation (Group I), and 32 were marked by the loss of prior FHM at a mean of 2.6 weeks later (Group II). Fetal tissue was removed by dilatation and suction curettage. Cytogenetic studies were performed from short-term cultures of dissected chorionic villi and/or sac. Result(s): Chromosomal aberrations were found in 75.0% of abortuses in Group I and 65.6% in Group II. Different types of chromosomal abnormalities were present in each of these groups. The maternal age-related trisomies which can progress to term (i.e., 13, 18, 21) were associated with early TVUS detection of FHM. The frequency of chromosomal abnormalities varied significantly with maternal age, with normal fetal karyotypes in 7 of 11 (63.6%) women <35 years, but only in 9 of 41 (22.0%) women ≥35 years despite the detection of FHM in 24 of 41 (58.5%) of these older women. Detection of FHM was associated with pregnancies continuing beyond the first trimester in 284 of 316 (90.0%) overall, but differed significantly with age (166 of 174 [95.4%] women <35 years vs. 118 of 142 [83.1%] women ≥35 years). Conclusion(s): Although the occurrence of chromosomal abnormalities in spontaneous demises did not differ according to TVUS detection of FHM, the types of aberrations were distributed differently. Since maternal age remains a significant factor in early fetal loss, TVUS detection of FHM should not be as reassuring for women ≥35 years as for younger women.

Abnormal renal function as a cause of false-positive biochemical screening for Down's syndrome

Estimation of the risk of Down’s syndrome is often based on a combination of human chorionic gonadotrophin (hCG) and alfa-fetoprotein (AFP) concentrations in conjunction with maternal age. 1 In 1995, four out of six consecutive pregnant women who had had a renal transplant seen at our hospital had positive tests and an amniocentesis was done. In all cases a normal fetal karyotype was found. This apparently high incidence of false-positive biochemical screening led us to investigate to what extent abnormal renal function, which often persists to some degree after renal transplantation, may modify the results of screening for Down’s syndrome. The six women in whom the above mentioned observations were made, and six more consecutive pregnant women who had a renal transplant and who became pregnant up to January, 1996, were enrolled. A control cohort of 12 age, parity, and gestational-age matched pregnant women was also enrolled. Serum concentrations of hCG, AFP, creatinine, creatinine and hCG clearances, and the estimated risk for Down’s syndrome were determined. Measurements of hCG were made with a solid-phase, two-site chemiluminescent enzyme immunometric assay for use with Immunolite Automated Analyzer. 2,3 To standardise for gestational age, the values of hCG are expressed in multiples of the median (MoM) of the values for normal pregnancies. A positive screening was considered as 1:270 or above, and fetal karyotyping was done in all cases. In the 12 renal-transplant women, the mean value for hCG was 3·00 (SD 1·59) MoM (range 0·74–5·81), and in control cases 1·12 (0·74) MoM (range 0·34–2·60, p<0·01) (table). A false-positive result of screening was observed in eight out of the 12 renal transplant women and in two out of the 12 controls. The positive results in the eight renal transplant women appears to be due to an abnormally elevated hCG. A good correlation was observed between the MoMs of hCG and the concentrations of serum creatinine (r=0·5746, p<0·01) and with creatinine clearances (r=0·5701, p<0·01). All fetal karyotypes were normal. We suspect that the difference in hCG between the two groups is probably due to abnormal renal function. These results may be increasingly relevant as the frequency of pregnancies in renal transplanted patients is increasing (over Variable Cases Controls p* n=12 (SD) n=12 (SD)

Transvaginal fetal biometry in early pregnancy.

To produce reference charts for fetal size with transvaginal sonography that are potentially helpful in evaluating normal and abnormal early pregnancies. A prospective cross-sectional study. 1081 normal singleton pregnancies with a normal fetal karyotype or normal healthy baby at delivery, at 9-16 weeks' gestation. Measurements included crown rump length, biparietal diameter, transverse cerebellar diameter, head and abdominal circumference, mean abdominal diameter, thoracic circumference, femur length, humerus length and foot length. The best description of the relationship between single ultrasonographic parameters and gestational age was achieved by polynomial regression analysis. All fetal biometric parameters correlated closely with gestational age. Biparietal diameter maintained the closest correlation with gestational age (r2 = 97.15, p < 0.001; y = -0.545 - 0.06x + 0.15x2); transverse cerebellar diameter showed the poorest correlation with gestational age (r2 = 88.17, p < 0.001). Reference ranges (5 degrees and 95 degrees percentile intervals) were constructed for all biometric parameters in relation to gestational age. Mean residuals are similar for all parameters with a very low range. These data provide normograms for first and early second trimester fetal measurements which may be of aid in the dating of pregnancies and can be useful in the early detection of genetic disorders affecting the growth of fetal structures.

Prenatal characteristics of congenital nephrosis: results of a survey.

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid alpha-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included. A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained. Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7-27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47-128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1-38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4-80.9). MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.

Mosaicism

Mosaicism detected in the cytogenetic analysis of chorionic villi or cultured amniocytes can present a difficult and at times impossible interpretative dilemma. The finding may be indicative of a generalized fetal mosaicism. However, in the majority of cases, the abnormal cell line is representative of either an in-vitro event or a chromosomal error that is restricted to the extra-embryonic tissues. Advances in laboratory medicine have provided insight into the determination of which cases of true mosaicism have the greatest risk of being clinically significant with regard to the fetal genotype and phenotype. Despite the presence of a normal fetal karyotype, certain chromosomes involved in confined placental mosaiciam may increase the risk of poor perinatal outcome or predispose the fetus or neonate to the adverse effects of genetic imprinting owing to the development of uniparental disomy.

Prenatal Characteristics of Congenital Nephrosis

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid α-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included.A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained.Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7–27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47–128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1–38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4–80.9).MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and una...

Maternal serum human chorionic gonadotropin as a marker for the delivery of low-birth-weight infants in women with unexplained elevations in maternal serum ?-fetoprotein

We wished to ascertain whether the measurement of maternal serum human chorionic gonadotropin (MShCG) in the serum of pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) would more precisely define those women at risk of adverse pregnancy outcomes. MShCG was measured in samples of serum obtained from women in the second trimester of pregnancy who had elevated MSAFP, normal Level II ultrasounds, and normal fetal karyotypes. Based on the characteristics of a receiver-operator curve for MShCG and birth weight, patients were divided into two groups and pregnancy outcomes were compared. Pregnant women with an unexplained elevation in MSAFP, who also had an abnormal MShCG (< or = 0.5 MoM > or = 2.5) were at significantly greater risk of delivering a low-birth-weight infant compared to women with a normal MShCG (43% and 15%, respectively; P = 0.013). They were also more likely to deliver a preterm infant (48% and 11.9%), respectively; P = 0.001). In the prediction of low birth weight, an abnormal MShCG had a sensitivity of 50%, a specificity of 81%, and a positive predictive value of 43%; in the detection of preterm delivery the values were 59%, 88%, and 48%, respectively. These findings suggest that in pregnant women with a second trimester unexplained elevation in MSAFP, abnormal MShCG levels may identify a group of women at high risk of preterm delivery or delivery of a low-birth-weight infant.

The roles of oligomenorrhoea and fetal chromosomal abnormalities in spontaneous abortions.

The pathogenesis of spontaneous abortions, other than fetal chromosomal abnormalities, is not fully understood. We examined the incidence of oligomenorrhoea in relation to fetal chromosomal analyses and ultrasonographic examination in women who aborted spontaneously. The data demonstrated that the incidence of oligomenorrhoea was higher in women with normal fetal karyotyped abortions, especially normal karyotyped anembryonic pregnancies, than in those with abnormal karyotyped abortions (34.0 versus 12.5%, P < 0.01). Furthermore, the incidence of oligomenorrhoea was inversely correlated with fetal size exclusively in abortions with normal fetal karyotypes. It is suggested that oligomenorrhoea, i.e. delayed ovulation, itself may be closely associated with sporadic spontaneous abortion.

Prenatal genetic services for Down's syndrome: access and provision in 1990–1991

Objective To examine access to and provision of prenatal genetic services relating to Down's syndrome.Design Retrospective review of obstetric casenotes.Sample Pregnancies involving Down's syndrome in England and Wales in 1990–1991 in women aged 38 or over. Information was obtained in 430 cases from a questionnaire completed by the obstetric team who were asked to provide details based only on documentation in the antenatal casenotes. The outcome of pregnancy was a termination in 268 (62%) cases, a liveborn child with Down's syndrome in 144(34%), a stillbirth in 9(2%), a miscarriage in 8(2%) and in one case was not known.Results Overall, prenatal diagnosis was not offered in 7% pregnancies (95% CI: 4.4–9.2%) with late booking given as the main reason. Of women offered prenatal diagnosis, 76% accepted (95% CI: 72.3–80.6%). Counselling was documented before prenatal diagnosis in 89% of cases (95% CI: 86.0–92.3%) and after the procedure, to discuss the results, in 73% (95% CI: 67.5–77.7%). In 10% of pregnancies terminated for Down's syndrome, fetal products were not sent to the laboratory. There was no report of a normal fetus having been terminated as a consequence of incorrect prenatal diagnosis. However, in 10% (95% CI: 5.9 to 14.0%) of cases examined in the laboratory, the diagnosis of Down's syndrome could not be confirmed. Details of prenatal diagnosis were not provided in five cases where a child with Down's syndrome was born. Of the remaining 139 livebirths, prenatal diagnosis was not offered in 27 (19%) cases, offered and declined in 92 (66%) and accepted in 20 (14%). In two cases a normal fetal karyotype was reported following prenatal diagnosis.Conclusions The study has demonstrated that in 1990–1991: 1. There were certain shortcomings in the documentation of antenatal care; 2. Late booking was the main factor precluding the offer of prenatal diagnosis to women aged 38 or over, and 3. The rate of confirmation of Down's syndrome in terminated fetuses was incomplete.

Fetal outcome in nuchal translucency with emphasis on normal fetal karyotype.

The aim of this study was to evaluate fetal outcome in fetuses with a nuchal translucency thickness of 3 mm or more, with emphasis on those with a normal karyotype. Between 1991 and 1994, a total of 104 pregnancies with suspected ultrasound abnormalities were referred to our prenatal unit for a fetal anomaly scan before 16 weeks of gestation. Of these 104 pregnancies, 54 were referred because of a nuchal translucency thickness of 3 mm or more. Data on these 54 pregnancies will be presented. Karyotyping was performed in all cases. An abnormal karyotype was found in 26/54 (48 per cent) pregnancies. A normal karyotype was established in the remaining 28 pregnancies. In this subset, five associated structural anomalies were detected at the first anomaly scan (9-15 weeks). Two pregnancies were terminated because of isolated nuchal translucency. In four of the continuing 21 pregnancies, additional structural anomalies were detected only at the second anomaly scan (16-20 weeks). Two of these were terminated because of bilateral renal dysplasia and a combination of exomphalos and ectopia cordis. Finally, 19 pregnancies progressed uneventfully and resulted in spontaneous delivery at a median gestational age of 40 weeks. A statistically significant difference in mean nuchal translucency thickness was found between cases with and without associated structural anomalies. This relationship indicates a more pronounced nuchal translucency thickness to be associated with a higher incidence of additional structural anomalies and, as a result, a poorer fetal outcome.

Adjusting the risk for trisomy 21 by a simple ultrasound method using fetal long-bone biometry

To establish the efficacy of second-trimester fetal long-bone biometry (femur, humerus, tibia, and fibula length) in detecting trisomy 21 and to generate tables for adjusting the risk of trisomy 21 according to long-bone biometry. Four long-bones--femur, humerus, tibia, and fibula--were measured ultrasonically in singleton fetuses before genetic amniocentesis. Fetuses with normal karyotypes were used to derive regression equations describing predicted lengths on the basis of the biparietal diameter measurement. The efficacy of each abnormally short bone, alone and in combination, was determined in 22 fetuses with trisomy 21 encountered during the study period. After the sensitivity and specificity of long-bone biometry were established, appropriate tables were generated by Bayes' theorem to adjust the risk of trisomy 21 in the second trimester depending on long-bone biometry. Of 515 patients between 14 and 23 weeks' gestation, 493 had normal fetal karyotypes and 22 had trisomy 21. The sensitivity of an abnormal ultrasound, as defined by the presence of one or more short bones, was 63.6% and the specificity was 78.5%. According to Bayes' theorem, genetic amniocentesis may not be recommended for women less than 40 years old in the presence of normal long-bone biometry (ie, all four bones normal). Second-trimester fetal long-bone biometry is useful in detecting trisomy 21 and may be used to adjust the a priori risk of both high- and low-risk women for trisomy 21 and, therefore, the need for genetic amniocentesis.

Maternal serum human chorionic gonadotropin as a marker for the delivery of Low-Birth-Weight Infants in women with unexplained elevations in maternal serum α-Fetoprotein

We wished to ascertain whether the measurement of maternal serum human chorionic gonadotropin (MShCG) in the serum of pregnant women with unexplained elevations of maternal serum α-fetoprotein (MSAFP) would more precisely define those women at risk of adverse pregnancy outcomes.MShCG was measured in samples of serum obtained from women in the second trimester of pregnancy who had elevated MSAFP, normal Level II ultrasounds, and normal fetal karyotypes. Based on the characteristics of a receiver-operator curve for MShCG and birth weight, patients were divided into two groups and pregnancy outcomes were compared.Pregnant women with an unexplained elevation in MSAFP, who also had an abnormal MShCG (≤0.5 MoM ≥2.5) were at significantly greater risk of delivering a low-birth-weight infant compared to women with a normal MShCG (43% and 15%, respectively; P = 0.013). They were also more likely to deliver a preterm infant (48% and 11.9%), respectively; P = 0.001). In the prediction of low birth weight, an abnormal MShCG had a sensitivity of 50%, a specificity of 81%, and a positive predictive value of 43%; in the detection of preterm delivery the values were 59%, 88%, and 48%, respectively.These findings suggest that in pregnant women with a second trimester unexplained elevation in MSAFP, abnormal MShCG levels may identify a group of women at high risk of preterm delivery or delivery of a low-birth-weight infant.

Studies on the cytogenetic and endocrinologic background of spontaneous abortion

To determine whether chronic menstrual irregularity with elevated LH levels has a role in spontaneous abortion. In 41 consecutively examined women with spontaneous abortions occurring within 11 complete gestational weeks, fetal chromosomal analyses were performed. The differences of endocrinologic background in relation to the result of fetal chromosomal analyses were investigated. Endocrinologic profiles, including menstrual history, basal hormone levels (LH, FSH, and PRL), ovarian morphology on ultrasound, and fetal chromosomal karyotypes. The women with normal fetal karyotypes compared with those with abnormal fetal karyotypes showed higher frequency of menstrual irregularity (47.1% versus 8.3%), elevated basal LH levels (7.42 +/- 5.12 versus 4.41 +/- 1.39 mIU/mL; conversion factor to SI unit, 1.00), and higher frequency of polycystic ovary (41.2% versus 8.3%). Elevated LH-polycystic ovary may be involved in the genesis of spontaneous abortions that are not explainable by fetal chromosomal abnormality.

Discrepant Karyotypes After Second- and Third-Trimester Combined Placentacentesis/Amniocentesis

Cytogenetic data are presented from a total of 1306 consecutive pregnancies with successful diagnosis obtained from both chorionic villi after short-time culture (CVS-SC) and amniotic fluid cell cultures (AC); samples had been taken simultaneously at combined placentacentesis (placental biopsy) and amniocentesis during the second (92.8 per cent) and third (7.2 per cent) trimesters. Concordant results were obtained in 1218 pregnancies with a normal karyotype and in 62 pregnancies with an aberrant fetal karyotype. Discrepant, i.e. false-positive and false-negative, results were found in 26 cases (2 per cent). From these data the accuracy of CVS-SC, defined as the proportion of all correct diagnoses, is calculated to be 98 per cent. Three non-mosaic and 14 mosaic false-positive results obtained after CVS-SC could not be confirmed by AC. Related to 1235 true normal fetal karyotypes, the specificity of CVS-SC, i.e. the proportion of normal karyotypes correctly diagnosed, amounts to 98.6 per cent. In nine pregnancies, an aberrant fetal karyotype detected after AC was missed by CVS-SC. The sensitivity of CVS-SC, i.e. the proportion of abnormal fetuses correctly diagnosed (62 out of 71), amounts to 87.3 per cent in our study group.

Failure of amniotic-fluid-cell growth: is it related to fetal aneuploidy?

We investigated outcome in patients whose amniotic-fluid-cell samples showed unexplained growth failure in culture. 32 of 7872 amniocentesis samples were classified as unexplained growth failures. 10 women did not have repeat cytogenetic testing, but among their pregnancies there were 4 abnormal outcomes (1 fetal bladder-outlet obstruction, 2 stillbirths, and 1 acardiac twin). Of the 22 patients who had repeat karyotypic analysis, 18 had normal fetal karyotypes. However, 4 fetuses were aneuploid (2 trisomy 21, 1 trisomy 13, and 1 Pallister-Killian syndrome).

Amniotic fluid erythropoietin levels in normal and Down's syndrome pregnancies

The aim of this study was to measure the levels of erythropoietin in amniotic fluid from normal and trisomy 21 pregnancies at 10 to 20 weeks gestation. Samples of amniotic fluid were collected from 142 women with singleton pregnancies after genetic amniocentesis; 110 had a normal fetal karyotype and 32 had trisomy 21. Erythropoietin was measured using a double antibody radioimmunoassay. Amniotic fluid erythropoietin levels in normal pregnancies increased from 10 weeks (mean 3.2 mU/ml; range < 2.0–6.3 mU/ml) to 20 weeks gestation (mean 7.9 mU/ml; range 2.0–11.5 mU/ml). There was a significant linear correlation between gestational age and erythropoietin levels ( r = 0.543; P < 0.0001). For the 32 patients with trisomy 21 pregnancies the median multiple of the median (MoM) was 1.11 (range 0.42–2.1). There was no difference between erythropoietin levels in amniotic fluid from normal and Down's syndrome pregnancies ( U = 2352, P = 0.75, 95% CI = −0.11, 0.18); (Mann-Whitney U-test).

The natural history of euploid pregnancies with first-trimester cystic hygromas

OBJECTIVES: Little information is available with regard to prognosis of euploid fetuses with first-trimester nuchal hygromas. To evaluate this population, the natural history, pregnancy outcome, and pediatric implication of this lesion were determined. STUDY DESIGN: Fetuses with cystic hygromas detected in the first trimester were retrospectively identified, and karyotype results were documented. Pregnancy outcome of those fetuses having a euploid karyotype was obtained, and physical examination of the live-born neonates and infants was performed by a clinical geneticist. RESULTS: A normal karyotype was identified in 22 (51%) of these pregnancies. Eighty-two percent of the euploid pregnancies were continued, with 89% of the fetuses surviving to the third trimester. Dysmorphic sequelae were documented in three children, including Noonan syndrome in one. CONCLUSION: In the presence of a normal karyotype fetuses with a first-trimester nuchal hygroma have an excellent prognosis. Normal outcome was seen in 80% of pregnancies carried to the third trimester. (AM J OBSTET GYNECOL 1994;170:1279-84.)

The natural history of euploid pregnancies with first -trimester cystic hygromas

OBJECTIVES: Little information is available with regard to prognosis of euploid fetuses with first-trimester nuchal hygromas. To evaluate this population, the natural history, pregnancy outcome, and pediatric implication of this lesion were determined. STUDY DESIGN: Fetuses with cystic hygromas detected in the first trimester were retrospectively identified, and karyotype results were documented. Pregnancy outcome of those fetuses having a euploid karyotype was obtained, and physical examination of the live-born neonates and infants was performed by a clinical geneticist. RESULTS: A normal karyotype was identified in 22 (51%) of these pregnancies. Eighty-two percent of the euploid pregnancies were continued, with 89% of the fetuses surviving to the third trimester. Dysmorphic sequelae were documented in three children, including Noonan syndrome in one. CONCLUSION: In the presence of a normal karyotype fetuses with a first-trimester nuchal hygroma have an excellent prognosis. Normal outcome was seen in 80% of pregnanCies carried to the third trimester. OBJECTIVES: Little information is available with regard to prognosis of euploid fetuses with first-trimester nuchal hygromas. To evaluate this population, the natural history, pregnancy outcome, and pediatric implication of this lesion were determined. STUDY DESIGN: Fetuses with cystic hygromas detected in the first trimester were retrospectively identified, and karyotype results were documented. Pregnancy outcome of those fetuses having a euploid karyotype was obtained, and physical examination of the live-born neonates and infants was performed by a clinical geneticist. RESULTS: A normal karyotype was identified in 22 (51%) of these pregnancies. Eighty-two percent of the euploid pregnancies were continued, with 89% of the fetuses surviving to the third trimester. Dysmorphic sequelae were documented in three children, including Noonan syndrome in one. CONCLUSION: In the presence of a normal karyotype fetuses with a first-trimester nuchal hygroma have an excellent prognosis. Normal outcome was seen in 80% of pregnanCies carried to the third trimester.

Quantification of human amniotic fluid constituents by high resolution proton nuclear magnetic resonance (NMR) spectroscopy.

We have investigated the ability of high-resolution proton NMR spectroscopy to provide a biochemical constituent screening of human amniotic fluid (AF). Proton NMR spectra were obtained at 300 MHz on AF from patients undergoing amniocentesis in the mid-trimester. Only AF from normal pregnancies (normal fetal karyotype, normal alpha-fetoprotein levels, normal birth outcome) was used in this study. The AF supernatant was lyophilized and resuspended in deuterated water containing 0.1 mM phosphate buffer and 6.02 mM disodium maleate. Identification of low molecular weight compounds was confirmed by two-dimensional NMR spectra (primarily correlated spectroscopy, or COSY) and standard addition techniques. A broad profile of compounds were 'NMR visible' in a single proton spectrum, including creatinine, glucose, organic acids (acetate, citrate, and lactate) and several amino acids (alanine, histidine, leucine, phenylalanine, tyrosine and valine). The proton spectrum was unaffected by prior freezing/thawing of AF samples. We were able to quantify compounds by comparison with an added concentration standard (maleate) at concentrations as low as 30 microM. Good agreement with literature values based on other analytical techniques was obtained.

Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) in the first trimester in association with abnormal fetal karyotype.

To assess the relation between maternal serum pregnancy associated plasma protein A (PAPP-A) in the first trimester and the outcome of pregnancy by karyotype. A retrospective study of PAPP-A levels in blood samples collected prior to chorionic villus sampling. Milan, Italy. Five hundred twenty-two women aged 20 to 47, at 7 to 11 weeks gestation, prior to undergoing chorionic villus sampling. Four hundred forty-five women had a pregnancy with a normal karyotype; in 30 pregnancies the karyotype was abnormal (including 14 cases of Down's syndrome and 7 of trisomy 18). Normal or abnormal fetal karyotype. Serum PAPP-A at 6 to 11 weeks gestation measured by radioimmunoassay. The median value of PAPP-A in the abnormal group was 0.27 multiples of the normal median (MoM). This is significantly lower than the median value in the normal group (1.01 MoM) (95% CI for the difference 0.46-0.84 MoM; P < 0.00001 Mann-Whitney test). There is an association between low levels of PAPP-A in the first trimester with chromosome anomalies. Screening by measurement of PAPP-A might detect 60% of cases of Down's syndrome in the first trimester with a false positive rate of 5%.