First trimester markers for pre-eclampsia: placental vs. non-placental protein serum levels

BACKGROUND/AIM: Parallel investigation, in a matched case-control study, of the association of different first-trimester markers with the risk of subsequent pre-eclampsia (PE). METHOD: The levels of different first trimester serum markers and fetal nuchal translucency thickness were compared between 52 cases of PE and 104 control women by non-parametric two-group comparisons and by calculating matched odds ratios. RESULTS: In univariable analysis increased concentrations of inhibin A and activin A were associated with subsequent PE (p < 0.02). Multivariable conditional logistic regression models revealed an association between increased risk of PE and increased inhibin A and translucency thickness and respectively reduced pregnancy-associated plasma protein A (PAPP-A) and placental lactogen . However, these associations varied with the gestational age at sample collection. For blood samples taken in pregnancy weeks 12 and 13 only, increased levels of activin A, inhibin A and nuchal translucency thickness, and lower levels of placenta growth factor and PAPP-A were associated with an increased risk of PE. CONCLUSIONS: Members of the inhibin family and to some extent PAPP-A and placental growth factor are superior to other serum markers, and the predictive value of these depends on the gestational age at blood sampling. The availability of a single, early pregnancy 'miracle' serum marker for PE risk assessment seems unlikely in the near future.     

Placental protein measurements in complicated pregnancies. I. Intrauterine growth retardation

Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein A (PAPP-A) were measured serially throughout pregnancy in 753 women who had a normal pregnancy when recruited during the second trimester. Thirty-three women were delivered of an infant with low birth-weight and with phenotypic features of intrauterine growth retardation (IUGR). The predictive value of an abnormal (less than 10th centile) hPL result (PVpos) in the identification of IUGR was between 28 and 32%, the sensitivity (36-54%) being greatest at 35 weeks gestation. The predictive value of a normal result (PVneg) was 87-96% at various stages of pregnancy, also greatest at 35 weeks gestation. For SP1, the sensitivity and predictive values were also greatest at 35 weeks gestation (PVpos, 20%; sensitivity, 32%; PVneg, 95%), but for PAPP-A these values were considerably less at all gestations. The trends in levels of hPL, SP1 and PAPP-A observed in individual patients with IUGR were not apparently related to any clinically recognizable feature of the pregnancy or the degree of fetal compromise, irrespective of whether the levels were within or outside the 80% confidence limits of the normal range or whether the levels fell from within the normal range. These data suggest that maternal hPL measurements are superior in the identification of IUGR in samples obtained at 30-35 weeks gestation.     

Placental protein measurements in complicated pregnancies. I. Intrauterine growth retardation

Summary. Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein l (SP1) and pregnancy-associated plasma protein A (PAPP-A) were measured serially throughout pregnancy in 753 women who had a normal pregnancy when recruited during the second trimester. Thirty-three women were delivered of an infant with low birth-weight and with phenotypic features of intrauterine growth retardation (IUGR). The predictive value of an abnormal (< 10th centile) hPL result (PVpos) in the identification of IUGR was between 28 and 32%, the sensitivity (36–54%) being greatest at 35 weeks gestation. The predictive value of a normal result (PVneg) was 87–96% at various stages of pregnancy, also greatest at 35 weeks gestation. For SP1, the sensitivity and predictive values were also greatest at 35 weeks gestation (PVpos, 20%; sensitivity, 32%; PVneg, 95%), but for PAPP-A these values were considerably less at all gestations. The trends in levels of hPL, SP1 and PAPP-A observed in individual patients with IUGR were not apparently related to any clinically recognizable feature of the pregnancy or the degree of fetal compromise, irrespective of whether the levels were within or outside the 80% confidence limits of the normal range or whether the levels fell from within the normal range. These data suggest that maternal hPL measurements are superior in the identification of IUGR in samples obtained at 30–35 weeks gestation.     

Use of prokineticin-1 (PROK1), pregnancy-associated plasma protein A (PAPP-A) and PROK1/PAPP-A ratio to predict adverse pregnancy outcomes in the first trimester: a prospective study

Introduction: To compare the predictive effectiveness levels of prokineticin-1 (PROK1), pregnancy-associated plasma protein A (PAPP-A) and the PROK1/PAPP-A ratio in the first trimester for preeclampsia (PE), foetal growth restriction (FGR), gestational diabetes mellitus (GDM) and spontaneous preterm birth (SPB).

Materials and methods: A total of randomly selected 162 pregnant women were included. Peripheral blood samples were obtained between 11^0/7 and 13^6/7 gestational weeks (GWs). All women were followed throughout the pregnancy and classified into five groups as having PE, FGR, GDM, SPB and uncomplicated pregnancies. The cut-off levels of the markers were identified to predict adverse outcomes.

Results: PROK1 predicted PE with 83.3% sensitivity, 85.7% specificity at a value of >293.4?pg/mL; at a value of >260.2?pg/mL, PROK1 predicted FGR with 85.7% sensitivity, 72.5% specificity in the first trimester. The area under receiver operating characteristic (ROC) curve of PAPP-A was lower than that of PROK1 and PROK1/PAPP-A in differentiating PE and FGR from the uncomplicated group (p?p?Conclusions: Elevated PROK1 in the first trimester is a more effective marker than PAPP-A in the prediction of PE and FGR. Lower PROK1 levels are associated with the development of SPB and GDM.     

Human placental lactogen is a first-trimester maternal serum marker of Down syndrome

BACKGROUND: Human placental lactogen (hPL) is synthesised by the placenta and found in maternal serum. We analysed the potential of hPL as a first-trimester maternal serum-screening marker for fetal Down syndrome (DS). MATERIALS AND METHODS: hPL was quantified by ELISA in 47 DS pregnancies and 136 controls in gestational weeks 8-13. Distributions of log multiples of the median (MoMs) were established. The quantity of hPL in DS screening was estimated using Monte Carlo simulation methods. RESULTS: The mean log10 MoM hPL was - 0.1995 (SD: 0.1993) in affected and 0.0026 (SD: 0.2129) in control pregnancies. This corresponds to a MoM of 0.63 in DS pregnancies. hPL correlated significantly with log10 MoM values of hCGbeta (r = 0.320) and PAPP-A (r = 0.590) in controls, but not with hCGbeta (r = 0.228) or PAPP-A (r = 0.090) in DS pregnancies. The inclusion of hPL in the double test (PAPP-A + hCGbeta) increased the detection rate from 67 to 75% for a false-positive rate of 5%. CONCLUSION: hPL is a DS screening marker that is applicable at weeks 9-13 and could be included in multiple marker first-trimester screening for DS.     

Measurement of plasma placental proteins and estriol in the detection of intrauterine growth retardation

This study was designed as an assessment of the clinical value of total estriol, placental lactogen (hPL), pregnancy specific glycoprotein (SP1), pregnancy-associated plasma protein-A (PAPP-A) and placental protein 5 (PP5), measured in a single sample of maternal serum, in the detection of intrauterine growth retardation (IUGR) in a large series of high risk pregnancies. Our results show the highest detection rate with SP1 (51%) and second highest with hPL (35%); estriol was less useful while PAPP-A and PP5 were of no value. However, there was 31% of false positives with SP1 compared with 14% for hPL. The best combination of the five parameters for the diagnosis of IUGR was achieved by measurement of both SP1 and hPL, with a low concentration of either protein indicating IUGR (sensitivity 63%, specificity 63%).     

Post-delivery oxidative stress in women with preeclampsia or IUGR

AIM: To compare oxidative stress in patients with preeclampsia (PE) or intrauterine growth restriction (IUGR) vs. normal pregnancy (controls) during 48 h after delivery. STUDY DESIGN: Women with singleton pregnancies were recruited immediately after delivery (gestational age >26.0 weeks). Women with PE or IUGR were matched with healthy controls by age, BMI, gestational age and delivery mode. Venous blood samples and urine samples were tested for oxidative stress products 24 h and 48 h after delivery. RESULTS: Plasma malondialdehyde (MDA) concentration 24 h after delivery was significantly higher in subjects with PE or IUGR (3.41+/-1.14 micromol/L, n=20) than in controls (2.91+/-0.82 micromol/L, n=38) (P=0.04). Urine iPF(2alpha)-VI declined from 24 to 48 h after delivery significantly in controls (P=0.006) and not in subjects with PE or IUGR (P=0.71). CONCLUSION: Of the markers tested only MDA is indicating higher oxidative stress in women with PE/IUGR than in normal pregnancy and only at 24 h after delivery. No consistent pattern of change in the oxidative stress markers exists between 24-48 h after delivery.     

Comparison of serum markers in first-trimester down syndrome screening

OBJECTIVE: To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency. METHODS: Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated. RESULTS: Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other. CONCLUSION: Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy. LEVEL OF EVIDENCE: II-2.     

Performance of a panel of maternal serum markers in predicting preeclampsia at 11-15 weeks' gestation

OBJECTIVE: We evaluated whether a discriminant model of prediction based on quantitative distribution of a panel of biomolecules in maternal serum can discriminate normal pregnancies from those who will develop preeclampsia (PE) prior to onset of clinical symptoms at 11-15 weeks' gestation. METHODS: Case control study encompassing 56 women destined to develop PE cases matched 1:3 for gestational age with 168 controls. After multiple of median (MoM) conversion of all available markers, comprising total Activin A (t-activin A), P-selectin, and vascular endothelial growth factor receptor (VEGFR) the combined likelihood ratios generated for each marker were used to calculate, for each patient enrolled in the study, the odds of being affected given a positive results (OAPR) of developing PE. For all the analyses performed, the type II error was < 20% with a type I error fixed at 5%. RESULTS: Data were expressed in MoM of controls. P-selectin was identified as the marker with the best discriminant ability between controls and PE, followed by (t-activin A). No significant differences in VEGFR were observed between cases and controls. By using a 3% prevalence of PE (or, about 1:33) we found that the median OAPR of developing PE for the 56 cases was 1:9 or 10% (1:1-1:417). The median OAPR of PE for controls was 1:40 or 2.5% (range, 1:6-1:4205). Detection rate of the statistical model, with a 5% false-positive rate was 59%. CONCLUSION: This analysis revealed that maternal serum markers assessed at the first and second trimester of pregnancy in asymptomatic patients can improve the early detection of cases at higher risk of developing PE.     

The efficacy of first-trimester PAPP-A and free beta hCG levels for predicting adverse pregnancy outcome

OBJECTIVE: To determine whether first-trimester measurements of maternal serum PAPP-A and free beta hCG levels were associated with adverse pregnancy outcomes. STUDY DESIGN: First trimester maternal serum free beta hCG and PAPP-A were measured in 490 singleton pregnancies. Pregnancies were followed by the fetal-maternal unit, and predictive efficacy of these markers for small for gestational age (SGA) babies, gestational diabetes mellitus and hypertensive disorders were analyzed by cut-off values determined by using a ROC analysis, and also, by using the fifth percentile as the cut-off value. RESULTS: The sensitivities for PAPP-A in predicting pregnancies with a SGA baby and those complicated by a hypertensive disorder were 49% and 73%, respectively, when optimal cut-off values were used. Specificities were 76% and 65%, respectively. Serum free beta hCG had no predictive value for individual pregnancy outcomes. CONCLUSION: Efficacy of first trimester maternal serum markers in predicting adverse pregnancy outcome is low. Even after optimization of cut-off values, these markers do not appear to be clinically acceptable as an effective tool for screening for adverse pregnancy outcomes.     

正常妊娠妇女与重度子痫前期患者止凝血功能的研究

目的:通过测定正常孕妇和重度子痫前期患者止凝血功能指标和分子标志物,从出凝血角度早期监测妊娠高血压疾病的发生。方法:2005年4月至2006年1月动态采集100例正常妊娠妇女孕10~14周、孕20~24周、孕30~34周和28例孕30~36周重度子痫前期患者外周血,检测止凝血功能指标:凝血酶时间(TT)、凝血酶原时间(PT)、纤维蛋白原(FIB)和止凝血分子标志物凝血酶原片断1+2(F1+2)、凝血酶调节蛋白(TM)、纤溶酶原激活物抑制剂(PAI-2)、血栓素B2(TXB2)等。结果:(1)正常妊娠妇女随孕周增加TT、PT缩短,PAI-2、TXB2增加,F1+2妊娠晚期与妊娠中期相比呈增加趋势(P<0.05),FIB和TM无统计学差异。(2)与正常妊娠晚期妇女相比,重度子痫前期患者TT延长,FIB减少;F1+2、PAI-2、TXB2呈增加趋势(P<0.01)。PT和TM无统计学差异。结论:止凝血功能指标可作为反映孕妇高凝状态的筛选指标,而止凝血分子标志物F1+2、PAI-2、TXB2可作为早期监测妊娠高血压疾病发生的敏感指标。     

Review: Biochemical markers to predict preeclampsia

Worldwide the prevalence of preeclampsia (PE) ranges from 3 to 8% of pregnancies. 8.5 million cases are reported yearly, but this is probably an underestimate due to the lack of proper diagnosis. PE is the most common cause of fetal and maternal death and yet no specific treatment is available. Reliable biochemical markers for prediction and diagnosis of PE would have a great impact on maternal health and several have been suggested. This review describes PE biochemical markers in general and first trimester PE biochemical markers specifically. The main categories described are angiogenic/anti-angiogenic factors, placental proteins, free fetal hemoglobin (HbF), kidney markers, ultrasound and maternal risk factors. The specific biochemical markers discussed are: PAPP-A, s-Flt-1/PlGF, s-Endoglin, PP13, cystatin-C, HbF, and α₁-microglobulin (A1M). PAPP-A and HbF both show potential as predictive biochemical markers in the first trimester with 70% sensitivity at 95% specificity. However, PAPP-A is not PE-specific and needs to be combined with Doppler ultrasound to obtain the same sensitivity as HbF/A1M. Soluble Flt -1 and PlGF are promising biochemical markers that together show high sensitivity from the mid-second trimester. PlGF is somewhat useful from the end of the first trimester. Screening pregnant women with biochemical markers for PE can reduce unnecessary suffering and health care costs by early detection of mothers at increased risk for PE, thus avoiding unnecessary hospitalization of pregnant women with suspect or mild PE and enabling monitoring of the progression of the disease thereby optimizing time for delivery and hopefully reducing the number of premature births.     

In vitro differentiation of villous trophoblasts from pregnancies complicated by intrauterine growth restriction with and without pre-eclampsia

Highly purified (>99.99%) primary villous cytotrophoblasts from uncomplicated pregnancies and pregnancies complicated with intrauterine growth restriction (IUGR) alone, IUGR with pre-eclampsia (IUGR-PE) and PE alone were cultured for 5days and the extent of differentiation into syncytiotrophoblasts measured in terms of syncytialisation and secretion of chorionic gonadotropin (hCG) and placental lactogen (hPL). Three separate phenotypes were observed: (1) normal and IUGR-PE cells showed low syncytialisation and secretion of hCG and hPL, (2) IUGR cells showed the highest levels of syncytialisation and secretion and (3) PE cells showed high syncytialisation but low secretion. These results strongly suggest IUGR, IUGR-PE and PE to be distinct conditions in which villous cytotrophoblasts are either exposed to different environments or are genetically different.     

Placental Protein-13 and Pregnancy-Associated Plasma Protein-A as First Trimester Screening Markers for Hypertensive Disorders and Small for Gestational Age Outcomes

Objective. To investigate the role of placenta protein 13 (PP13) and pregnancy-associated plasma protein-A (PAPP-A) in hypertensive disorders and small for gestational age (SGA) during first trimester of pregnancy. Methods. In this case–control study, first trimester serum samples (11⁺⁰ to 13⁺⁶ weeks) were retrieved from frozen storage of which 452 were from normal pregnancies and 47 samples were identified to have pregnancies with at least one of the following adverse outcomes: SGA, preeclampsia (PE), hemolysis, elevated liver enzymes, and low platelets (HELLP), or gestational hypertension (GH). PP13 concentrations were measured by a new AutoDELFIA method. Levels of PAPP-A were measured for a first trimester screening program using Kryptor analyzer. Results. First trimester levels of PAPP-A are significantly lower in cases of SGA, PE, and most subgroups including HELLP. Levels of PP13 were not found to differ between control and affected pregnancies. Conclusion. PP13 needs to be studied further as our results contrast the majority of previous studies.     

Second-trimester levels of pregnancy-associated plasma protein-A and free beta-hCG in pregnancies with trisomy 13

OBJECTIVE: To examine the levels of free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in second-trimester maternal serum from pregnancies affected by trisomy 13 and compare these with the known reduced levels of these markers in first-trimester cases in an attempt to better understand the pathophysiology of changes in marker levels in chromosomally abnormal pregnancies between the first and second trimester. METHODS: Using the Kryptor immunoassay system, we measured free beta-hCG and PAPP-A in 32 singleton pregnancies affected by trisomy 13 between 14 and 20 weeks of gestation. Using medians established in a previous study, these results were compared against 450 normal singleton pregnancies over the same gestational range. The data were combined with data from 82 cases of trisomy 13 previously examined in the first trimester (11-13 weeks) and an analysis of analyte trend was performed. RESULTS: The median free beta-hCG in multiples of the appropriate gestational median (MoM) in the second-trimester samples was not significantly different from the controls (1.15 (95% CI 0.827-1.651) vs 1.00). The median PAPP-A MoM in the second-trimester samples was significantly lower (p<0.001) than in controls (0.25 (95% CI 0.164-0.373) vs 1.00). Seventy-eight percent of cases were below the 5th centile of normal for PAPP-A. The combined cases in the first trimester had a median free beta-hCG MoM of 0.58 (95% CI 0.454-0.668) and a median PAPP-A MoM of 0.26 (95% CI 0.218-0.320). For PAPP-A, there was no significant change in median across the gestational period of 11 to 20 weeks, whilst for free beta-hCG, there was a significant increase with gestation (r=0.458, p<0.001). CONCLUSIONS: Although PAPP-A levels are reduced in trisomy 13 pregnancies in the second trimester, this isolated lower marker value is unlikely to be of value in screening for trisomy 13 in the second trimester. The aetiology of reduced levels of PAPP-A in cases with trisomy 13 may be similar to that in cases with trisomy 18, but different from that in cases with trisomy 21 since the temporal pattern in trisomies 13 and 18 are different from that in trisomy 21.     

Vascular endothelial growth factor, its receptors, and the tie receptors in the placental bed of women with preeclampsia, diabetes, and intrauterine growth retardation

Placental bed vascular function is compromised in pregnancies complicated by preeclampsia (PE), intrauterine growth retardation (IUGR), and maternal diabetes mellitus (DM). We performed an immunohistochemical analysis of vascular endothelial growth factor (VEGF), its receptors (VEGFR) -1 and -2, and the Tie-1 and -2 receptors in cryostat tissue sections of the placental bed from healthy women (n = 5) and women with PE (n = 5), IUGR (n = 5), and DM (n = 5). VEGF immunoreactivity was stable between the study groups. VEGFR-1 immunoreactivity in the myometrial vascular smooth muscle cells was strongest in the controls. In the myometrial cells, the strongest VEGFR-2 immunoreactivity was seen in women with IUGR. In the decidual vascular endothelial cells, the strongest Tie-1 immunoreactivity was observed in healthy women and in those with DM. Alterations in the placental bed expression of VEGFR-1, VEGFR -2, and Tie-1, but not of VEGF and Tie-2, may be associated with PE, IUGR, or DM.     

Placental protein and hormone measurements in twin pregnancy

Summary. Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1), pregnancy-associated plasma protein A (PAPP-A), placental protein 5 (PP5) and total oestriol (E3) were measured serially in 35 twin pregnancies during the third trimester. Eighteen pregnancies had major complications including dysmaturity of one or both fetuses in nine, premature labour in six, and placental abruption in three. Serum levels of all five variables were higher than in singletons, this distinction being greatest for hPL and lowest for SP1 and E3. The levels of hPL, PP5 and E3 just before delivery were significantly correlated with the total birthweight, a correlation with placental weight being evident only for hPL and PP5. A significant correlation between the five biochemical variables at 33–34 weeks was only seen between hPL and PAPP-A. Protein and hormone levels in. the abnormal twin pregnancies were not apparently different from those in the normal twin pregnancies. These data suggest that only hPL levels biochemically reflect this extreme of fetal and placental growth, but that neither the levels of hPL nor any of the other biochemical indices examined are altered in abnormalities in twin pregnancy     

Maternal serum levels of dimeric inhibin A in pregnancies affected by trisomy 21 in the first trimester.

Dimeric inhibin A was measured in maternal serum samples from 45 pregnancies affected by trisomy 21 and 493 samples from unaffected pregnancies at 10-14 weeks of gestation. Inhibin A levels in affected pregnancies were compared with levels of free beta-hCG and PAPP-A in the same series. In the trisomy 21 group, the median multiple of the median (MoM) inhibin A was not significantly elevated (1.28 vs 1.00) with only 15.5% being above the 95th centile. In contrast, the median MoM free beta-hCG was significantly increased (2.05 vs 1.00) with 36% above the 95th centile and PAPP-A was significantly reduced (0.49 vs 1.00) with 42% below the 5th centile. Inhibin A levels in the trisomy 21 group were significantly correlated with gestational age such that median levels rose from 1.04 at 11 weeks to 1.30 at 12 weeks and 1.67 at 13 weeks. These findings suggest that first trimester biochemical screening for trisomy 21, which is currently optimised using maternal serum free beta-hCG and PAPP-A and fetal nuchal translucency, will not benefit from the inclusion of inhibin A.     

Placental protein and hormone measurements in twin pregnancy

Maternal serum levels of human placental lactogen (hPL), schwangerschaftsprotein 1 (SP1), pregnancy-associated plasma protein A (PAPP-A), placental protein 5 (PP5) and total oestriol (E3) were measured serially in 35 twin pregnancies during the third trimester. Eighteen pregnancies had major complications including dysmaturity of one or both fetuses in nine, premature labour in six, and placental abruption in three. Serum levels of all five variables were higher than in singletons, this distinction being greatest for hPL and lowest for SP1 and E3. The levels of hPL, PP5 and E3 just before delivery were significantly correlated with the total birthweight, a correlation with placental weight being evident only for hPL and PP5. A significant correlation between the five biochemical variables at 33-34 weeks was only seen between hPL and PAPP-A. Protein and hormone levels in the abnormal twin pregnancies were not apparently different from those in the normal twin pregnancies. These data suggest that only hPL levels biochemically reflect this extreme of fetal and placental growth, but that neither the levels of hPL nor any of the other biochemical indices examined are altered in abnormalities in twin pregnancy.     

Second-trimester maternal pregnancy-associated plasma protein a and inhibin a levels in fetal trisomies

OBJECTIVE: The aim of this study was to determine whether fetal trisomy is associated with altered levels of second-trimester maternal pregnancy-associated plasma protein A (PAPP-A) and inhibin A. METHODS: Maternal serum PAPP-A and inhibin A concentrations were measured at 15-17 weeks of gestation in 14 singleton pregnancies with fetal trisomy and in 56 matched pregnant controls. RESULTS: PAPP-A levels in the trisomy group were significantly lower than in controls. The inhibin A level with fetal trisomy 21 was slightly higher than the control group, but levels were not different between trisomies 18 and 13 and controls. CONCLUSION: Fetal trisomies 21, 18, and 13 are associated with a reduction in second-trimester maternal PAPP-A levels; trisomies 18 and 13 are not associated with increased inhibin A levels, unlike trisomy 21.