Maternal Serum Free β-hCG Research Articles

Association between birth weight and first-trimester free β–human chorionic gonadotropin and pregnancy-associated plasma protein A

To assess the relationship between first-trimester maternal serum PAPP-A and free beta-hCG and birth weight. Observational study. Teaching hospital. Singleton pregnancies (n = 1,630) at 10-14 weeks of gestation. Fluorimetric immunoassays for maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG. Customized birth weight percentiles, calculated taking into account maternal height, weight, ethnic origin, parity, smoking status, and fetal gender. There was a significant positive correlation between birth weight and PAPP-A, but not free beta-hCG levels. Maternal serum levels of PAPP-A were significantly lower in small-for-gestation (SGA) newborns than in control subjects and were significantly higher in large-for-gestation (LGA) newborns than in control subjects. Maternal serum free beta-hCG levels were lower in pregnancies complicated by pre-eclampsia than in normotensive ones. Multivariable analysis found PAPP-A to be an independent predictor of absolute birth weight, SGA, and LGA. Free beta-hCG was found to be an independent predictor of gestational hypertension and pre-eclampsia. Neither of the two markers was associated with preterm delivery. Maternal serum PAPP-A levels in the late first trimester of pregnancy are associated with subsequent fetal growth (including both physiologic variation and abnormal growth), and decreased free beta-hCG is more predictive of hypertensive disorders of pregnancy.

Screening for Trisomy 21 with Maternal Age, Fetal Nuchal Translucency and Maternal Serum Biochemistry at 11–14 Weeks: A Regional Experience from Germany

Objective: To examine the efficacy of first trimester screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT), maternal serum free β-human chorionic gonadotropin (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in a regional setting [maternity unit of the Women’s University Hospital, Hannover Medical School (study center); two regional private centers for prenatal diagnosis and human genetics; laboratory for prenatal diagnosis and human genetics]. Methods: Fetal NT, crown-rump length, maternal serum free β-hCG and PAPP-A were measured at 11–14 weeks of gestation. Risk calculation was carried out using the FMF computer algorithm. The patients were informed and counseled about possible invasive test options if the risk was 1 in 300 or greater. Fetal outcome was obtained by questionnaires given to the patients or sent to their gynecologists. The detection and false-positive rates for the different screening strategies were calculated. Results: Pregnancy outcome was obtained in 2,497 cases, of which 2,196 cases had completed first trimester screening with NT and maternal serum biochemistry and 301 additional cases had NT measurement only. The median age was 32.5 years. In our population 11 affected fetuses were found. The estimated risk for trisomy 21 was 1 in 300 or greater in 64, 82, 88 and 88% of affected fetuses using maternal age alone, in combination with nuchal translucency, with maternal serum biochemical markers or with both NT and biochemical markers for a false-positive rate of 28.2, 5.1, 15.3 and 4.0%. Conclusions: First trimester screening using maternal age, NT, free β-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is associated with a sensitivity of about 90% for 5% false-positive patients.

Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free β-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks

To examine whether in pregnancies with fetal trisomy 21 the level of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation is independent of the presence or absence of tricuspid regurgitation and to estimate the performance of a screening test that combines tricuspid regurgitation with fetal nuchal translucency (NT) thickness and serum free beta-hCG and PAPP-A. The study population comprised 77 trisomy 21 and 232 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. In all cases the fetal karyotype was determined by chorionic villus sampling (CVS), which was carried out at the request of the parents after first-trimester screening for trisomy 21 by fetal NT and maternal serum free beta-hCG and PAPP-A. Immediately before chorionic villus sampling, fetal echocardiography was performed and the presence or absence of tricuspid regurgitation was determined by pulsed wave Doppler ultrasonography. The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present tricuspid regurgitation was examined. We examined two screening strategies: first, integrated first-trimester screening in all patients and second, first-stage screening of all patients using fetal NT and maternal serum free beta-hCG and PAPP-A followed by second-stage assessment of tricuspid regurgitation only in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first stage. Tricuspid regurgitation was observed in 57 (74.0%) of the trisomy 21 fetuses and in 16 (6.9%) of the chromosomally normal fetuses. There were no significant differences in median maternal age, median gestational age, free beta-hCG multiples of the median (MoM) and PAPP-A MoM in trisomy 21 fetuses with and without tricuspid regurgitation. The modeled detection rates of trisomy 21 for fixed false positive rates of 1%, 2% and 5% in screening by maternal age, fetal NT thickness and maternal serum free beta-hCG and PAPP-A and assessment of tricuspid flow in all cases were 87%, 90% and 95%. In the two-stage approach, the estimated detection rate was 91% and the false positive rate was 2.6%. There is no relationship between tricuspid regurgitation and the levels of maternal serum free beta-hCG and PAPP-A in cases with trisomy 21. An integrated sonographic and biochemical test at 11 + 0 to 13 + 6 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 2-3%.

First trimester combined screening for chromosomal defects: Our results in a population with a high percent of women aged 35 or older

Background. Screening strategies for the detection of aneuploidies should be performed by every Prenatal Diagnosis Service. Several screening approaches have been developed, reaching detection rates of at least 85% for a 5% false-positive rate. Our experience in a population with a high percent of women aged 35 or older using combined screening is presented.Methods. From July 1999 to October 2004, we conducted a prospective study of screening for fetal aneuploidies among pregnant women between 10 and 14 weeks. Risks for aneuploidy were calculated by combined screening, using maternal age, maternal serum free-βhCG, pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency. The result was considered positive if the combined risk exceeded the cut off risk of 1/270.Results. Screening was completed in 4538 singleton pregnancies. The mean maternal age was 31.08 years, and in 25.9% the age was 35 years or greater. The detection rate was 76.9% (30/39) for all aneuploidies with a false-positive rate of 3,6%. For trisomy 21, the detection rate was 73.7% (14/19) with a false-positive rate of 3.6%. At a 5% false-positive rate, the sensitivity of combined screening and nuchal translucency were 78.9% and 63.2% respectively.Conclusions. First trimester combined screening is efficient, and its application can be assumed in a tertiary hospital.

Prediction of pregnancy complications by first‐trimester maternal serum PAPP‐A and free β‐hCG and with second‐trimester uterine artery Doppler

Previous studies have shown an association between low first trimester maternal serum free beta-hCG and PAPP-A and subsequent development of pregnancy complications. Similarly, uterine artery Doppler in the late second trimester has shown that high impedance to flow is associated with increased risk for preeclampsia and fetal growth restriction. The objective of this study is to determine whether there is an association between the maternal serum concentration of PAPP-A and free beta-hCG at 11-13(+6) weeks with the uterine artery pulsatility index (PI) at 22-24 weeks, and secondly, to compare the screening characteristics of the two methods in the prediction of adverse pregnancy outcome. Maternal serum PAPP-A and free beta-hCG at 11-13(+6) weeks and uterine artery PI at 22-24 weeks were measured in 4390 women with singleton pregnancies. Pregnancies with chromosomal defects or fetal anomalies were excluded. The biochemical and Doppler measurements were compared between those with normal outcome and those resulting in spontaneous preterm delivery, pre-eclampsia and fetal growth restriction (FGR). Detection rates using a combination of the biochemical and Doppler measurements were investigated. In the pregnancies resulting in pre-eclampsia (n = 64) and FGR (n = 172), the median PAPP-A was lower (0.844 and 0.813 MoM), the median uterine artery mean PI was higher (1.56 and 1.18) but the median free betahCG was not significantly different (0.923 and 0.933 MoM) than in the normal outcome group. In the preterm delivery group (n = 159), the median free beta-hCG (0.944 MoM) and uterine artery mean PI (1.06) were not significantly different from normal but the median PAPP-A (0.928 MoM) was significantly lower than normal. In screening for pre-eclampsia, the detection rate, for a 5% false-positive rate, was 14.1% for PAPP-A, 54.7% for uterine artery mean PI and 62.1% for a combination of PAPP-A and uterine artery mean PI. Maternal serum PAPP-A at 11-13(+6) of gestation is significantly lower in adverse pregnancy outcomes. The combination of first trimester serum PAPP-A and uterine artery mean PI at 22-24 weeks improves the screening efficacy for the prediction of pre-eclampsia.

First trimester combined screening for chromosomal defects: Our results in a population with a high percent of women aged 35 or older

AbstractBackground. Screening strategies for the detection of aneuploidies should be performed by every Prenatal Diagnosis Service. Several screening approaches have been developed, reaching detection rates of at least 85% for a 5% false-positive rate. Our experience in a population with a high percent of women aged 35 or older using combined screening is presented.Methods. From July 1999 to October 2004, we conducted a prospective study of screening for fetal aneuploidies among pregnant women between 10 and 14 weeks. Risks for aneuploidy were calculated by combined screening, using maternal age, maternal serum free-βhCG, pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency. The result was considered positive if the combined risk exceeded the cut off risk of 1/270.Results. Screening was completed in 4538 singleton pregnancies. The mean maternal age was 31.08 years, and in 25.9% the age was 35 years or greater. The detection rate was 76.9% (30/39) for all aneuploidies with a false-p...

First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement?

To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies. Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice. In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses). The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced.

The effect of vaginal bleeding on maternal serum PAPP-A, free β-hCG, and nuchal translucency. A population based screening study (the FASTER trial)

Vaginal bleeding in the first trimester may result in a disruption in the maternal-fetal interface with subsequent transfer of hormones into the maternal circulation. Elevated maternal serum concentrations of AFP have been observed in the first and second trimester in women with a history of first trimester vaginal bleeding. Our goal was to examine the effect of first trimester vaginal bleeding on first trimester serum levels of PAPP-A, free β-hCG, and nuchal translucency (NT) using a prospectively-collected large database.

A Comparison between Maternal Serum Free β-Human Chorionic Gonadotrophin and Pregnancy-Associated Plasma Protein A Levels in First-Trimester Twin and Singleton Pregnancies

Objectives: To determine the levels of first-trimester free β-human chorionic gonadotrophin (free βhCG), pregnancy-associated plasma protein A (PAPP-A) and nuchal translucency (NT) in twin pregnancies. Methods: The study included 93 patients with twin pregnancy and 4,977 with singletons who underwent first-trimester testing using free βhCG, PAPP-A and NT at 10–13 weeks of gestational age. Results: In twin pregnancies, the maternal serum free βhCG level was 2.18 higher and the PAPP-A level was 2.38 higher than in singleton pregnancies. These marker levels were significantly higher than the expected 2.0 multiples of the median (MoM). In contrast, NT values did not differ between twins and singletons. Conclusion: These data may be used to establish first-trimester combined screening for twin pregnancies.

Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years experience

Objective To evaluate the performance of screening for fetal trisomy 21 in the first trimester of twin pregnancies by a combination of maternal serum biochemistry and ultrasonography. Design Three year retrospective review of screening performance. Setting District General Hospital maternity unit. Population All women booked to receive routine antenatal care at Harold Wood Hospital between 1 June 1998 and 30th September 2001. The population included 13,940 women of all ages presenting with pregnancies between 10 weeks 3 days and 13 weeks 6 days gestation. Of these, 230 had a twin pregnancy. Methods Women booked into the clinic were offered screening using a combination of maternal serum free β-hCG and pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. Women at increased risk of carrying a fetus with trisomy 21 or trisomy 13/18 (≥1 in 300 at sampling) were offered counselling and an invasive diagnostic procedure. Follow up of the outcome of all pregnancies was carried out. For women who on examination were at 14 weeks of gestation or greater, or for women presenting as late bookers beyond 14 weeks, screening was performed in the same time frame using only maternal serum free β-hCG and α-fetoprotein. Main outcome measures The first trimester detection rate for trisomy 21 and all aneuploides, false positive rate, uptake of screening, uptake of invasive testing in women identified at increased risk and fetal loss rates after invasive testing. Results Overall, 97.4% of the women with twins (224/230) accepted first trimester screening. The rate of detection of trisomy 21 was 75% (3/4). Fetal death at presentation was found in 3.4% of fetuses (16/460). Of women who accepted screening, 4.3% (10/230) presented too late for fetal nuchal translucency measurement and 10.0% of women (23/230) presented too early. A risk for trisomy 21 was calculated for each fetus based on the individual fetal nuchal translucency thickness and the maternal biochemistry. The false positive rate among those eligible for first trimester screening was 9.0% (19/206) of pregnancies and 6.9% of fetuses (28/412). Uptake of invasive testing was 59% (10/17) with chorionic villus sampling in eight cases and amniocentesis in two. No fetal loss occurred within 28 days of chorionic villus sampling and no loss occurred after amniocentesis. One case of trisomy 21 was identified for every three invasive procedures. Conclusion First trimester screening for trisomy 21 in twin pregnancies is both theoretically possible and practically achievable using a combination of nuchal translucency thickness and maternal serum biochemistry. However, dilemmas for the mother and health professionals when both nuchal translucency thickness measurements are normal might suggest that greater reliance be placed on the nuchal translucency thickness risk alone when counselling women about invasive testing.

Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience

Objective To evaluate the performance of a one-stop multidisciplinary clinic of screening for fetal chromosomal anomalies in the first trimester of pregnancy by a combination of maternal serum biochemistry and ultrasonography. Design Retrospective review of screening performance. Setting District General Hospital maternity unit. Population All women booked for routine antenatal care at Harold Wood Hospital between 1 June 1998 and 31 May 2001. The population included 12,339 women with singleton pregnancies presenting at 10–14 weeks of gestation. Methods Women were offered screening using a combination of maternal serum free β-hCG and pregnancy associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. Those with an estimated risk of ≥1 in 300 of carrying a fetus with trisomy 21 or trisomy 18 or trisomy 13 were offered the option of an invasive diagnostic test. Follow up of the outcome of all pregnancies was carried out. Main outcome measures Uptake of screening and invasive testing, detection rate for fetal chromosomal abnormalities and false positive rate. Results The uptake of first trimester screening was 97.5% and the uptake of invasive testing in the increased risk group was 77%. The rate of detection of trisomy 21 was 92% (23 of 25), of trisomy 13 or 18 was 100% (all 15) and of all aneuploidies was 96% (49 of 51). The false positive rate was 5.2%. Conclusion First trimester screening for trisomy 21 and other aneuploidies can be delivered in an efficient manner in a one-stop multidisciplinary clinic. The detection rates are far better than can be achieved by second trimester serum screening.

First Trimester Maternal Serum Free Human Chorionic Gonadotropin as a Predictor of Adverse Pregnancy Outcome

Objective: The purpose of this study was to evaluate whether abnormal levels of first trimester maternal serum free human chorionic gonadotropin (β-hCG) are predictive of adverse pregnancy outcomes. Methods: The study included 1,622 consecutive patients with singleton pregnancies who underwent first trimester Down syndrome screening using nuchal translucency, and maternal serum free β-hCG and pregnancy-associated plasma protein-A. Patients with fetal anomalies or chromosome aberrations were excluded from the study. The incidences of various adverse pregnancy outcomes were evaluated according to maternal serum free β-hCG levels. Outcome variables included spontaneous miscarriage, proteinuric and non-proteinuric pregnancy-induced hypertension, fetal growth restriction, intrauterine fetal demise, spontaneous preterm delivery, oligohydramnios and placental abruption. Results: No significant differences were noted between groups for any of the demographic variables. The only statistically significant result was an increase in the relative risk for spontaneous miscarriage (RR = 6.33) at free β-hCG <0.2 multiples of the medians. No other statistically significant result was noted for the other adverse outcomes or for the overall complication rate. Conclusion: Low free β-hCG is associated with a higher incidence of spontaneous miscarriage but is a poor predictor of other pregnancy complications.

Screening for trisomy 21 by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11–14 weeks: a German multicenter study

Objective: To examine the effectiveness of screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum biochemistry using free β-humanchorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation.Methods: This was a multicenter study of screening for trisomy 21 by a combinationof maternal age, fetal NT and maternal serum free β-hCG and PAPP-A at 11-14 weeks of gestation, using the methodology developed by the Fetal Medicine Foundation. The distribution of estimated risksfor trisomy 21 was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 were calculated.Results: In total, 3864 singleton pregnancies with live fetuses at 11-14weeks were examined and the fetal NT and maternal serum free β-hCG and PAPP-A were successfully measured in all cases. The median maternal age was 33 (range 15-46) years and, in 1271 (35.8%), the agewas 35 years or more, the median gestation at screening was 12 (11-14) weeks and the median fetal crown-rump length was 64 (range 45-84) mm. The fetal NT was above the 95th centile in 73.7% (14 of 19) oftrisomy 21 and in 4.8% (169 of 3505) of normal pregnancies. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free β-hCG and PAPP-A was 1 in 300 or greater in 6.6%(233 of 3505) of normal pregnancies, in 84.2% (16 of 19) of those with trisomy 21 and 88.9% (24 of 27) of those with other chromosomal defects.Conclusions: In Germany, the results of screeningfor chromosomal defects by measurement of fetal NT and maternal serum biochemistry, in centers with appropriately qualified sonographers, are similar to those reported in the UK using the same methodology.

Age related detection and false positive rates when screening for Down's Syndrome in the first trimester using fetal nuchal translucency and maternal serum free βhCG and PAPP-A

Objective To determine how first trimester detection rates for Down's Syndrome vary with maternal age and to calculate the predictive value of an increased risk report at various maternal ages. Design Mathematical modelling of first trimester screening performance using fetal nuchal translucency and maternal serum free βhCG and pregnancy associated plasma protein-A (PAPP-A). Methods From within the Gaussian distributions of each marker in normal pregnancies and those affected by Down's Syndrome a series of 15,000 marker multiple of the medians were obtained for each group. These markers were then used to calculate the risks of Down's Syndrome using maternal ages ranging from 15 to 49 and the background risk of Down's Syndrome at each age. Using a 1 in 300 risk cutoff (at time of sampling) the false positive rate and detection rate was assessed at each year of maternal age. The predictive value of a positive result was calculated using Baye's theorem. Outcome measures False positive rates and detection rates at each year of maternal age between 15 and 49; the predictive value of a positive result for each maternal age between 15 and 49. Results At 15 years of age the detection rate was 77% at a 1.9% false positive rate, 84% at a 4% false positive rate at age 30, rising to 100% at a 67% false positive rate at age 49. The probability of Down's Syndrome once identified with an increased risk was 1:34 at 15 years, 1:29 at 30 years and 1:6 at 49 years. Conclusions As with second trimester biochemical screening, the detection rate and false positive rate vary considerably with age. However, detection rates across all ages are significantly higher than with second trimester screening. The risk of a positive screening result being a Down's pregnancy is considerably greater than with second trimester screening with an average probability of 1:29, compared with 1:55 in the second trimester. This information may be useful in counselling women with an increased risk result in first trimester screening.

Age related detection and false positive rates when screening for Down's syndrome in the first trimester using fetal nuchal translucency and maternal serum free betahCG and PAPP-A.

To determine how first trimester detection rates for Down's Syndrome vary with maternal age and to calculate the predictive value of an increased risk report at various maternal ages. Mathematical modelling of first trimester screening performance using fetal nuchal translucency and maternal serum free betahCG and pregnancy associated plasma protein-A (PAPP-A). From within the Gaussian distributions of each marker in normal pregnancies and those affected by Down's Syndrome a series of 15,000 marker multiple of the medians were obtained for each group. These markers were then used to calculate the risks of Down's Syndrome using maternal ages ranging from 15 to 49 and the background risk of Down's Syndrome at each age. Using a 1 in 300 risk cutoff (at time of sampling) the false positive rate and detection rate was assessed at each year of maternal age. The predictive value of a positive result was calculated using Baye's theorem. False positive rates and detection rates at each year of maternal age between 15 and 49; the predictive value of a positive result for each maternal age between 15 and 49. At 15 years of age the detection rate was 77% at a 1.9% false positive rate, 84% at a 4% false positive rate at age 30, rising to 100% at a 67% false positive rate at age 49. The probability of Down's Syndrome once identified with an increased risk was 1:34 at 15 years, 1:29 at 30 years and 1:6 at 49 years. As with second trimester biochemical screening, the detection rate and false positive rate vary considerably with age. However, detection rates across all ages are significantly higher than with second trimester screening. The risk of a positive screening result being a Down's pregnancy is considerably greater than with second trimester screening with an average probability of 1:29, compared with 1:55 in the second trimester. This information may be useful in counselling women with an increased risk result in first trimester screening.

The influence of parity and gravidity on first trimester markers of chromosomal abnormality

We have studied changes in first trimester fetal nuchal translucency (NT) and maternal serum free β-hCG and PAPP-A with gravidity and parity in 3252 singleton pregnancies unaffected by chromosomal abnormality or major pregnancy complications. We have shown that gravidity and parity is associated with a small but progressive decrease in fetal NT and a small but progressive increase in free β-hCG and PAPP-A. None of these small changes with increasing gravidity or parity are statistically significant and hence correction for these variables is not necessary when considering first trimester screening for chromosomal abnormalities. Copyright © 2000 John Wiley & Sons, Ltd.

Screening for trisomy 13 by fetal nuchal translucency and maternal serum free ?-hCG and PAPP-A at 10-14 weeks of gestation

In 42 cases of trisomy 13 at 10–14 weeks of gestation, compared with 947 controls, the median multiple of the median (MoM) of maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein A (PAPP-A) was significantly decreased (0.506 MoM and 0.248 MoM respectively), whilst fetal nuchal translucency was increased (2.872 MoM). In 38% and 71% of cases of trisomy 13 maternal serum free β-hCG and PAPP-A was below the 5th centile of the appropriate normal range for gestation and in 62% of cases the nuchal translucency was above the 95th centile. When combined together in a multivariate algorithm with maternal age, 90% of cases of trisomy 13 could be detected at a 0.5% false positive rate or 84% at a 0.1% false positive rate. We conclude that specific trisomy 13 risks should be part of developing risk algorithms combining maternal serum biochemistry and nuchal translucency for use in first trimester screening alongside those for trisomy 21 and trisomy 18. Copyright © 2000 John Wiley & Sons, Ltd.

Second-trimester prenatal screening for Down syndrome and the relationship of maternal serum biochemical markers to pregnancy complications with adverse outcome

In a group of 26 524 control pregnancies and a group of 3728 pregnancies affected by one or more of the pregnancy complications of low birthweight, intra-uterine growth restriction (IUGR), preterm delivery and stillbirth, I have compared the relative risk of occurrence of these complications in pregnancies which had a raised maternal serum AFP (>2.0 MoM), raised maternal serum free beta-hCG (>2.0 MoM), low AFP (<0.5 MoM), low free beta-hCG (<0.5 MoM), combined raised AFP and free beta-hCG (>2.0 MoM), and in those with an increased Down syndrome risk (1 in 250 or greater). In the low birthweight group, only an increased AFP and decreased free beta-hCG showed significance with relative risks of 1.6 and 2.1. In the IUGR group, also only an increased AFP and decreased free beta-hCG showed significance with relative risks of 1.6 and 2.3. In the preterm delivery group, raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta-hCG showed significance with relative risks of 3.8, 1.8 and 6.2. In the stillbirth group, raised AFP, reduced free beta-hCG, and combined elevated AFP and free beta-hCG showed significance with relative risks of 4.5, 2,4 and 7.2. An isolated raised free beta-hCG or an increased Down syndrome risk were not associated with an increased relative risk for any of the pregnancy complications investigated. However, apart from the six to seven-fold increased risk when both AFP and free beta-hCG are above 2.0 MoM, suggesting increased risk of preterm delivery or impending fetal death, the clinical utility of such significant differences is probably poor.

Second trimester levels of pregnancy associated plasma protein‐A in cases of trisomy 18

In a study of 70 cases of trisomy 18 and 450 matched controls in the second trimester we have measured the maternal serum levels of the analytes alpha feto protein (AFP), free β-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A). We have found the median multiple of the median (MoM) of maternal serum free β-hCG to be significantly lower (0.327) than normal, as was the level of AFP (0.600). Levels of PAPP-A were reduced even further (0.108). Of the markers associated with trisomy 18 at this time PAPP-A was the most discriminatory, being lower than the 5 per cent centile of normal in 93 per cent of cases, compared with 57 per cent of cases for free β-hCG and 32 per cent of cases for AFP. Combining free β-hCG and PAPP-A or all three markers with maternal age would have the ability to detect 74 per cent of cases at a 0.5 per cent false positive rate (or 64 per cent at a 0.1 per cent false positive rate). Unlike in cases of trisomy 21, the low PAPP-A values observed in the first trimester are continued into the second trimester. Whether the good discriminatory power of PAPP-A can be realized in second trimester screening programmes will depend on developing two stage screening algorithms. This approach is unlikely to be better than the excellent detection rates achievable with free β-hCG, PAPP-A and nuchal translucency in the first trimester. Copyright © 1999 John Wiley & Sons, Ltd.

Second trimester levels of pregnancy associated plasma protein-A in cases of trisomy 18

In a study of 70 cases of trisomy 18 and 450 matched controls in the second trimester we have measured the maternal serum levels of the analytes alpha feto protein (AFP), free beta-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A). We have found the median multiple of the median (MoM) of maternal serum free beta-hCG to be significantly lower (0.327) than normal, as was the level of AFP (0.600). Levels of PAPP-A were reduced even further (0.108). Of the markers associated with trisomy 18 at this time PAPP-A was the most discriminatory, being lower than the 5 per cent centile of normal in 93 per cent of cases, compared with 57 per cent of cases for free beta-hCG and 32 per cent of cases for AFP. Combining free beta-hCG and PAPP-A or all three markers with maternal age would have the ability to detect 74 per cent of cases at a 0.5 per cent false positive rate (or 64 per cent at a 0.1 per cent false positive rate). Unlike in cases of trisomy 21, the low PAPP-A values observed in the first trimester are continued into the second trimester. Whether the good discriminatory power of PAPP-A can be realized in second trimester screening programmes will depend on developing two stage screening algorithms. This approach is unlikely to be better than the excellent detection rates achievable with free beta-hCG, PAPP-A and nuchal translucency in the first trimester.