Maternal Serum Pregnancy-associated Plasma Protein A Levels Research Articles

First‐trimester biochemical markers of aneuploidy and the prediction of small‐for‐gestational age fetuses

To examine the clinical utility of the first-trimester biochemical markers of aneuploidy in their ability to predict subsequent delivery of a small-for-gestational age (SGA) infant. We examined singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the expected normal median (MoM) for a pregnancy of the same gestation. The association between free beta-hCG and PAPP-A and the incidence of SGA were assessed by comparing the relative incidence at MoM cut-offs and birth-weight centile cut-offs. At various marker levels the likelihood ratios (LR) for SGA were also calculated after excluding other adverse pregnancy complications. There were 46,262 pregnancies resulting in live births with birth weight at or above the 10(th) centile, and 3,539 below the 10(th) centile for gestation (SGA). There was a significant inverse association between the risk for SGA and maternal serum PAPP-A MoM but not free beta-hCG MoM. At the 5(th) centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for SGA below the 10(th), 5(th) and 3(rd) centiles of normal were 2.70, 3.21 and 3.66 and the respective detection rates for SGA were 12.0%, 14.0% and 16.0%. Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk for subsequent delivery of an SGA infant.

Low Maternal Serum Levels of Pregnancy-associated Plasma Protein-A During the First Trimester are Associated with Subsequent Preterm Delivery with Preterm Premature Rupture of Membranes

To assess the relationship between the first-trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels and pregnancies complicated by preterm delivery. The correlation between PAPP-A levels and gestational age at delivery was analyzed by linear regression. The probabilities of low PAPP-A multiples of the median (MoM) levels between preterm delivery and control population were analyzed by logit model. A positive correlation was noted between the first-trimester PAPP-A MoM levels and gestational age at delivery between 34-38 weeks (p < 0.001). Lower PAPP-A MoM level had a significantly higher likelihood of preterm delivery (p < 0.05). When preterm premature rupture of membranes (PPROM) and preterm labor (PTL) were analyzed separately, there was an increasing likelihood of PPROM with decreasing PAPP-A MoM levels (p < 0.05), but not for PTL with intact membranes. Low maternal serum PAPP-A levels during the first trimester may reflect a trophoblast invasion defect in the maternal-fetal interface, resulting in subsequent preterm delivery, particularly in those of PPROM.

Dose dependency between cigarette consumption and reduced maternal serum PAPP‐A levels at 11–13+6 weeks of gestation

To examine whether in smokers there is a significant dose dependency between the number of cigarettes per day and levels of free ss-hCG and pregnancy-associated plasma protein A (PAPP-A) at 11-13(+6) weeks of gestation. This was a retrospective analysis of the maternal serum free ss-hCG and PAPP-A levels in relation to the maternal smoking status in 109 263 chromosomally normal singleton pregnancies that had undergone first-trimester screening for Down syndrome by a combination of fetal nuchal translucency thickness and maternal serum biochemistry. There were 95 287 nonsmokers and 13 976 cigarette smokers. The overall median PAPP-A MoM among cigarette smokers was 0.827, which was 19.6% lower than the value of 1.029 in nonsmokers (p < 0.0001 for log(10) MoM). The respective values for beta-hCG MoM were 1.003 for smokers and 1.035 for nonsmokers (p < 0.0001 for log(10) MoM) which corresponds to a reduction of 3.1%. There was a significant inverse relationship between the number of cigarettes per day and the level of PAPP-A MoM (r = 0.989, p < 0.0001) but not the level of free beta-hCG MoM (r = 0.733; p = 0.098). Using a statistical modeling approach we found that the screen-positive rate when correcting the PAPP-A MoM by an all or nil smoking factor was reduced by only 0.1% (3.75 vs 3.85%) when compared to correcting with a factor related to the smoking dose per day. In first-trimester screening for Down syndrome by maternal serum PAPP-A and free beta-hCG the impact of correcting for the dose dependant rather than the all or nil effect of smoking is marginal. However, a dose dependent correction improves the accuracy of the individual patient-specific risk.

Maternal serum free ß‐hCG and PAPP‐A in patients with habitual abortion‐influence on first‐trimester screening for chromosomal abnormalities

To explore if maternal serum free beta-hCG and pregnancy-associated plasma protein A (PAPP-A) levels in the first-trimester of pregnancy are altered in patients with habitual abortions and if there is an effect on first-trimester screening for Down syndrome. A retrospective study was conducted on 913 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome. Maternal serum PAPP-A and free beta-hCG were compared between patients with (n = 64) and without habitual abortions (n = 849). The medians +/- SD log(10) MoM of PAPP-A and free beta-hCG +/- SD in patients with and without habitual abortions were 0.063 +/- 0.28 versus - 0.014 +/- 0.27 and - 0.001 +/- 0.27 versus - 0.018 +/- 0.31, with a p value of 0.042 and 0.87, respectively. The screen positive rate setting the cut off at 1:350 looking at the background risk for trisomy 21 was 71.4% in women with and 81.2% in women without habitual abortion, after combined first-trimester screening it was 7.8% in women with and 10.1% in women without recurrent abortion. Patients with habitual abortions have slightly increased maternal serum PAPP-A levels in the first-trimester. This marginal difference seems not to effect risk calculation in combined first-trimester screening for trisomy 21.

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.

First‐trimester combined screening for trisomy 21 in a predominantly Chinese population

To examine the effectiveness of first-trimester fetal trisomy 21 screening using a combination of maternal age, nuchal translucency thickness (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels in a predominantly Chinese population in Hong Kong. This was a prospective study over a 1.5-year period of 2990 women who underwent combined screening for trisomy 21 between 11+0 and 13+6 weeks of gestation in a university fetal medicine unit. NT was measured according to the criteria set by The Fetal Medicine Foundation (FMF), maternal serum free beta-hCG and PAPP-A levels were measured, and the risk of trisomy 21 was calculated using The FMF's algorithm. Fetal karyotyping was advised when the risk was 1 : 300 or above. All subjects were followed up for pregnancy and fetal outcome. Of the 2990 women who underwent the screening program, 99% were Chinese. There were 57 twin pregnancies, giving a total of 3047 fetuses. Thirty-one percent of the women were 35 years old or above. One hundred and eighty-five (6.1%) fetuses were screen-positive; this included 14 cases of trisomy 21 and 17 cases of other chromosomal abnormalities. The positive predictive value was 16.7%. Among the 2862 screen-negative fetuses, only 18 (0.6%) cases had an unknown fetal outcome. There were no cases in which trisomy 21 was missed and the infant was liveborn. First-trimester combined screening for fetal trisomy 21 is highly effective among Chinese subjects.

Correlation between first trimester fetal bone length and maternal serum pregnancy-associated plasma protein-A (PAPP-A)

Pregnancy-associated plasma protein-A (PAPP-A) is produced by the embryo and placenta during pregnancy, and its maternal serum concentrations are related to subsequent fetal growth. Evidence from animal models and in vitro experiments suggests that PAPP-A is particularly involved in the regulation of bone development. The aim of this study was to assess the correlation between late first trimester fetal bone length and maternal serum levels of PAPP-A. In a cross-sectional observational study, ultrasound measurements of fetal long bones and fluorimetric immunoassays for maternal serum PAPP-A were performed in 514 singleton pregnancies at 10-14 weeks of gestation. There were 501 uncomplicated pregnancies. There were significant correlations between PAPP-A values and length of humerus, femur and tibia [r values 0.12 (P = 0.01), 0.11 (P = 0.01) and 0.10 (P = 0.03), respectively]. The association with the length of ulna and foot did not reach statistical significance (r values 0.08 and -0.03, respectively). Maternal serum PAPP-A levels at 10-14 weeks of gestation are significantly associated with the length of fetal long bones such as humerus, femur and tibia. This provides further evidence that PAPP-A may be involved in the regulation of bone development.

First‐trimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death

To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict future fetal loss. We examined 54,722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness, maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the expected normal median for a pregnancy of the same gestation (MoM) and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length (CRL). The association between free beta-hCG, PAPP-A and delta NT and the incidence of fetal loss prior to 24 weeks, at or after 24 weeks or at any time, was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratio (LR) for fetal loss was also calculated. The rate of fetal loss increased with decreasing maternal serum free beta-hCG and PAPP-A and increasing delta NT. At the 5th centile of the normal outcome group for free beta-hCG (0.41 MoM) the odds ratio for fetal loss before 24 weeks, at or above 24 weeks and at any gestation was 3.1, 1.8 and 2.6, respectively. The respective values for the 5th centile of PAPP-A (0.415 MoM) were 3.3, 1.9 and 2.8 and for the 95th centile of delta NT they were 2.5, 1.9 and 2.2, respectively. There was almost no correlation between reduced levels (<or=0.50 MoM) of PAPP-A and reduced levels of free beta-hCG in either the normal pregnancy group (r = 0.041) or the group with fetal death (r = 0.072), indicating relatively independent prediction by either biochemical marker. Low levels of maternal serum PAPP-A and free beta-hCG and increased fetal NT are associated, in the absence of an abnormal karyotype, with an increased risk of impending fetal death. The likelihood ratio profiles provided at various levels of PAPP-A or free beta-hCG may be of some help in counseling women with such results and raise awareness among health-care professionals for increased surveillance in such cases.

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 maternal serum level of pregnancy‐associated plasma protein‐A is an independent predictor of fetal maxillary bone length

To derive a nomogram of fetal maxillary bone length (MAX) for a Chinese population and to study whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) is an independent predictor of fetal MAX. This was a prospective observational study over 10 months examining Chinese women with a singleton pregnancy who attended the first-trimester screening program for Down syndrome. The subjects had the fetal crown-rump length (CRL), nuchal translucency, MAX, maternal serum PAPP-A and free beta-human chorionic gonadotropin (fbeta-hCG) levels measured. A nomogram of MAX was derived using normal pregnancies with reliable dates. The correlations between MAX, CRL, PAPP-A and fbeta-hCG levels were studied, after correction for gestational dependency using Z-score transformation for the ultrasound markers (Z-MAX and Z-CRL), and logarithmic transformation of multiple of gestation-specific medians for the biochemical markers (log10PAPP-A multiples of the median (MoM) and log10fbeta-hCG MoM), using the Pearson test and multiple regression analysis. During the study period, 607 Chinese women met the inclusion criteria. The mean gestational age at the first-trimester screening was 12 + 4 weeks (SD, 4 days). Curve estimation analysis showed that a linear relationship fit best between MAX and CRL (MAX (mm) = -0.01 + 0.101 * CRL (mm); r = 0.826; P < 0.0001), and between MAX and gestational age (MAX (mm) = -8.465 + 0.170 * gestational age (day); r = 0.754; SD = 0.71; P < 0.0001). There were significant positive correlations between Z-MAX and Z-CRL (r = 0.627; P = < 0.0001), Z-MAX and log10PAPP-A MoM (r = 0.239; P = < 0.0001). Multiple regression analysis showed that both Z-CRL (P = < 0.0001) and log10 PAPP-A MoM (P = 0.048) were independent predictors for Z-MAX. Both CRL and maternal levels of PAPP-A are independent predictors of the fetal MAX measured during the first trimester. The positive correlation between PAPP-A levels and fetal MAX is consistent with the known biological function of PAPP-A on bone growth. This association must be adjusted for when both PAPP-A and MAX are combined for screening of Down syndrome.

OC26.06: First trimester maternal serum level of pregnancy associated plasma protein A is an independent factor of fetal maxillary bone length

To derive a normogram of fetal maxillary bone length for a Chinese population and to study whether first trimester maternal serum levels of pregnancy associated plasma protein A (PAPP-A) is an independent factor of fetal maxillary bone length. This was a prospective study of 607 Chinese women with a singleton pregnancy who attended our first trimester screening for Down syndrome programme. The subjects had the fetal crown-rump length (CRL), nuchal translucency, maxillary bone length, maternal serum PAPP-A and free beta-hCG (fβ-hCG) levels measured. A normogram of maxillary bone length was derived using normal pregnancies without date problem. The correlations between maxillary length, CRL, PAPP-A and fβ-hCG levels were studied, after correction for gestational dependency using z-score transformation for the ultrasound markers (z-MAX and z-CRL), and logarithmic transformation of multiple of medians (MoM) for the biochemical markers. Positive correlations were further analysed with multiple regression. The mean gestational age at screening was 124 weeks (SD: 4 days). Curve estimation analysis showed that a linear relationship fit best between maxillary bone length and CRL (r = 0.826; p < 0.001), and between maxillary length and gestational age (r = 0.754; SD = 0.71; p < 0.001). There were significant positive correlations between z-MAX and z-CRL (r = 0.627; p = < 0.001), z-MAX and log10PAPP-Amom (r = 0.239; p = < 0.001). Multiple regression analysis showed that both z-CRL (p = < 0.001) and log10PAPP-A < STARTSUBmom (p = 0.048) were independent factors for z-MAX. Both CRL and maternal levels of PAPP-A are independent factors for the fetal maxillary length measured during the first trimester. The positive correlation between PAPP-A levels and fetal maxillary length is consistent with the known biological function of PAPP-A on bone growth. This association must be adjusted for when both PAPP-A and maxillary length are combined for screening of Down syndrome.

Maternal serum biochemistry at 11-13+6 weeks in relation to the presence or absence of the fetal nasal bone on ultrasonography in chromosomally abnormal fetuses: an updated analysis of integrated ultrasound and biochemical screening

Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-hCG and pregnancy associated plasma protein-A (PAPP-A) at 11-13(+6) weeks of gestation is associated with a detection rate of 90%, for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21 the nasal bone is not visible at the 11-13(+6) week scan and that the frequency of absence of nasal bone differs in different ethnic groups. In addition, there is a relationship between absent nasal bone and nuchal translucency thickness. In a preliminary study we showed that while PAPP-A levels were lower and free beta-hCG levels were higher in trisomy 21 fetuses with an absent nasal bone, this difference was not statistically different. In fetuses with trisomy 13 and trisomy 18, there is also a high (57 and 67%) incidence of an absent nasal bone. The aim of this present study was to extend our examination of whether the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone in cases with trisomy 21 and to ascertain if any differences exist in cases with trisomies 13 and 18. This study data comprised 100 trisomy 21 singleton pregnancies at 11-13(+6) weeks of gestation from our previous study and an additional 42 cases analysed as part of routine OSCAR screening. A total of 34 cases with trisomy 18 and 12 cases with trisomy 13 were also available. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free beta-hCG and PAPP-A were measured using the Kryptor rapid random access immunoassay analyser (Brahms Diagnostica AG, Berlin). The distribution of maternal serum free beta-hCG and PAPP-A in chromosomally abnormal fetuses with absent and present nasal bone was examined. The nasal bone was absent in 29 and present in 13 of the new trisomy 21 cases and in 98 (69%) and 44 respectively in the combined series. For the trisomy 18 cases, the nasal bone was absent in 19 (55.9%) cases and in 3 (25%) of cases of trisomy 13. There were no significant differences in median maternal age, median gestational age, NT delta, free beta-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone, and similarly for those with trisomies 13 or 18. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 96% of cases with trisomy 21. For a false-positive rate of 0.5%, the detection rate was 88%. There is no relationship between an absent fetal nasal bone and the levels of maternal serum PAPP-A or free beta-hCG in cases with trisomies 13, 18 or 21. An integrated sonographic and biochemical test at 11-13(+6) weeks can potentially identify about 88% of trisomy 21 fetuses for a false-positive rate of 0.5%.

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.

Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome.

First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction.

The possible effect of assisted reproduction on first-trimester screening for trisomy 21 was examined by fetal nuchal translucency thickness (NT), maternal serum free beta-human chorionic gonadotrophin (HCG) and pregnancy-associated plasma protein-A (PAPP-A). Parameters were measured at 11-14 weeks in 411 singleton pregnancies achieved by controlled ovarian stimulation, including 220 that had undergone IVF. Results were compared with 1233 singleton pregnancies conceived spontaneously. In the IVF pregnancies, the median fetal NT was not significantly different from that in controls, whilst the median free beta-HCG was significantly increased, and PAPP-A was significantly decreased. In the intracytoplasmic sperm injection group, fetal NT and free beta-HCG values were not significantly different from those in controls, but PAPP-A was significantly decreased. In those pregnancies achieved by ovarian stimulation, neither fetal NT, free beta-HCG nor PAPP-A were significantly different from the control group. In IVF pregnancies, screening for trisomy 21 by fetal NT, maternal serum free beta-HCG and PAPP-A levels may be associated with a 1.2% higher false-positive rate than in natural conception.

The influence of smoking on maternal serum PAPP-A and free beta hCG levels in the first trimester of pregnancy.

In an analysis of 3111 singleton pregnancies routinely screened in the first trimester with nuchal translucency, free beta hCG and pregnancy associated plasma protein A (PAPP-A) smoking has been found to occur in 20.8 per cent of pregnant women. When the individual marker levels were assessed in smokers and non-smokers, levels of PAPP-A were reduced in smokers by some 15 per cent. Despite free beta hCG levels being reduced by 10-14 per cent in the second trimester of smoking women, in the first trimester period this is not evident. Simulation studies would suggest that in smokers the detection of trisomy 21 using free beta hCG, PAPP-A and maternal age will be reduced by some 5 to 6 per cent compared with that of the general population.

First trimester maternal serum pregnancy-associated plasma protein A and pregnancy-specific beta 1-glycoprotein in fetal trisomies.

To examine the potential value of maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta 1-glycoprotein (SP1) in the detection of fetal trisomy. Cross-sectional study. The Harris Birthright Research Centre For Fetal Medicine, King's College Hospital Medical School, London, UK and Division of Maternal-Fetal Medicine, Jefferson Medical College, Philadelphia, USA. Maternal serum PAPP-A and SP1 concentrations were measured at 10 to 13 weeks gestation in samples from 42 pregnancies with fetal trisomy (trisomy 21, n = 29; trisomy 18, n = 9; trisomy 13, n = 4) and in samples from 210 matched controls. In controls, both maternal serum PAPP-A and SP1 increased significantly with gestation and in trisomic fetuses levels of both hormones were reduced. However, discriminant analysis demonstrated that SP1 did not contribute significantly in the distinction between trisomic and control pregnancies. Although levels of PAPP-A were reduced throughout the gestational range examined (10 to 13 weeks), especially in cases with fetal trisomy 21, the deviation was more pronounced at 10 to 11 weeks than at 12 to 13 weeks gestation. In 45% of pregnancies with fetal trisomy 21 and 70% of pregnancies with trisomies 18 or 13 maternal serum PAPP-A levels at 10 to 11 weeks gestation were below the 5th centile of the normal range. Maternal serum PAPP-A concentration in the first trimester of pregnancy may prove to be useful in the prediction of risk for fetal trisomies.