Could first-trimester assessment of placental functions predict preeclampsia and intrauterine growth restriction? A prospective cohort study

Objective: To examine the role of first-trimester uterine artery Doppler, serum β-hCG and pregnancy-associated placental protein-A (PAPP-A) in prediction of preeclampsia and IUGR.

Methods: A total of 100 pregnant women in the 11–14 weeks’ gestation were examined using uterine artery Doppler, serum β-hCG and PAPP-A. All women were followed-up for development of preeclampsia or IUGR.

Results: A total of 94 women completed the study of which 7 (7.4%) developed complications. Uterine artery PI and RI were significantly higher whereas serum β-hCG and PAPP-A levels were significantly reduced in patients who developed complications when compared with those who did not. Uterine artery PI had the highest sensitivity (100%) but a low specificity (56% and 45%) in prediction of preeclampsia and IUGR, respectively. Adding PAPP-A to uterine artery PI elevated the specificity into 94.44% and 95.51%, respectively. Combined PI and β-hCG elevated the specificity into 88.89% and 89.89%, respectively.

Conclusion: Our study suggests that first-trimester uterine artery impedance, as measured by Doppler ultrasound as well as low serum biomarkers (β-hCG and PAPP-A) can be used for prediction of preeclampsia and IUGR. The most sensitive is uterine artery PI. Adding β-hCG to PI improves specificity in prediction of both preeclampsia and IUGR. Uterine artery PI plus PAPP-A is the best combination for prediction of both preeclampsia and IUGR     

First trimester maternal serum pregnancy-associated plasma protein-A is a predictive factor for early preterm delivery in normotensive pregnancies

Abstract

In this study, we investigated whether the concentrations of pregnancy-associated plasma protein-A (PAPP-A) or free β-hCG (fβhCG) in the first trimester can identify women at increased risk of subsequent preterm delivery in the absence of hypertensive disorders. Preterm and early preterm deliveries are defined as those deliveries before completing 37 and 34 weeks, respectively. A total of 868 women were enrolled into this study. According to the level of the markers, the patients were evaluated in three groups: 1 – maternal serum level ≤5th percentile, 2 – between 5th and 95th percentiles, 3 – ≥95th percentile. In the group of patients with a PAPP-A level ≤5th percentile [≤0.35 multiples of the median (MoM)], mean gestational age (GA) at delivery, mean birth weight and the number of the cases with early preterm delivery were significantly lower than the others. Mean level of PAPP-A was significantly lower in cases with early preterm than term deliveries (0.58?±?0.32 versus1.09?±?0.69; p?=?0.01). Maternal serum level of fβhCG did not show significant difference between these groups (0.84?±?0.45 versus 1.17?±?0.77; p?=?0.15). Low levels of maternal serum PAPP-A (≤0.35 MoM) (Odds ratio?=?7; 95% confidence interval 1.8–27.7; p?=?0.0048) significantly predicted early preterm delivery in normotensive pregnancies. Women with low levels of PAPP-A at first trimester have a higher risk of early preterm delivery even in the absence of hypertensive disorders.     

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.     

Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex

OBJECTIVE: The aim of the present study was to evaluate the effects of fetal gender on serum human chorionic gonadotropin (hCG) and testosterone in normotensive and preeclamptic pregnancies. METHODS: The study consisted of 137 women with singleton pregnancies in the third trimester. Seventy-three pregnancies were uncomplicated; among those were 35 male and 38 female fetuses. Sixty-four pregnancies were complicated by preeclampsia; among those were 33 male and 31 female fetuses. Human chorionic gonadotropin and total testosterone were measured in maternal peripheral blood. RESULTS: In male-bearing pregnancies, maternal hCG and testosterone serum levels were significantly higher in preeclamptic than normotensive mothers (P <.001). In female-bearing pregnancies, testosterone levels were significantly higher in preeclamptic than normotensive mothers (P <.001), whereas the hCG levels were not significantly different. Male-bearing preeclamptic women had significantly higher testosterone levels than female-bearing preeclamptic women (P <.02), whereas the hCG levels were not significantly different. In uncomplicated pregnancies the hCG levels were significantly higher in female-bearing than in male-bearing mothers (P <.005), whereas the testosterone levels were not significantly different. CONCLUSION: In preeclamptic pregnancies with male fetuses, the maternal serum hCG levels were significantly higher than in uncomplicated pregnancies. Total testosterone levels were significantly higher in pregnancies with either gender and significantly higher in male-bearing than in female-bearing pregnancies. This may indicate an androgen influence on the pathophysiologic mechanism of preeclampsia.     

Eliminating first trimester markers: will replacing PAPP-A and βhCG miss women at risk for small for gestational age?

Abstract

Objective: Placental analytes are traditionally used for aneuploidy screening, although may be replaced by cell-free fetal DNA. Abnormal analytes also identify women at risk for small for gestational age (SGA). We sought to quantify the proportion of women at risk for SGA by low pregnancy-associated plasma protein-A (PAPP-A) or βhCG who would not otherwise be identified by maternal risk factors.

Methods: We studied first-trimester PAPPA-A and βhCG from 658 euploid singleton pregnancies from a prospective longitudinal cohort. Analytes were standardized for gestational age in multiples of the median (MoM). SGA was defined as birthweight z-score ≤?1.28. Maternal risk factors included chronic hypertension, pre-gestational diabetes and age ≥40.

Results: Mean GA was 38.8?±?1.9 weeks; 6.8% had a SGA infant. Low PAPP-A and βhCG were identified in 48 (7.4%) and 9 (1.4%) of pregnancies, respectively, of whom 18.9% were SGA (OR 3.0, 95% CI 1.4–6.3). 88% did not have risk factors for SGA. Among women with no risk factors, low PAPP-A was a significant predictor of SGA (OR 3.3, 95% CI 1.5–7.4).

Conclusion: Most women with abnormal analytes did not have risk factors for SGA. Eliminating PAPP-A and βhCG may present missed opportunities to identify women at risk for SGA.     

Down syndrome biochemical markers and screening for preeclampsia at first and second trimester: correlation with the week of onset and the severity

OBJECTIVES: To estimate the combined screening performance of first and early second trimester prenatal serum markers for Down syndrome, in screening for the development of preeclampsia, and analyze the correlation among marker levels, week of onset, and severity of the disease. METHODS: A retrospective cohort study was carried out on 32 women with preeclampsia and 3044 controls. Serum samples from these pregnancies were assayed for pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotrophin (hCG), and inhibin-A. A likelihood ratio and the odds of being affected given a positive result (OAPR) of various combinations of markers were calculated and receiver operating characteristic (ROC) curves analysis was performed. RESULTS: In the pregnancies that subsequently developed preeclampsia, first trimester PAPP-A concentration was significantly lower and concentrations of early second trimester inhibin-A and hCG significantly elevated. Levels of early second trimester uE3 and AFP were not significantly altered. We also found that inhibin-A correlates with both onset of the disease and the severity. CONCLUSION: Down syndrome biochemical markers levels are altered in those patients who subsequently developed preeclampsia and may be a useful screening test for preeclampsia. Inhibin-A is the most predictive marker and correlates with the severity of subsequent preeclampsia and inversely with the week of occurrence of preeclampsia.     

Impact of inherited thrombophilias on first and second trimester maternal serum markers for aneuploidy

Objective: To evaluate first and second-trimester maternal serum markers in pregnancies complicated with inherited thrombophilias. Methods: A case-control study was conducted in 50 pregnancies complicated with hereditary thrombophilia and 100 control pregnancies. Results: Each woman with inherited thrombophilia received low molecular weight heparin (LMWH) throughout her pregnancy. Gravidity, parity, number of first-trimester and second-trimester abortions, and rate of adverse pregnancy outcomes (APO) were significantly higher in the thrombophilia group compared to the control group (P < 0.001 for all). Among the thrombophilia group median values of pregnancy associated placental protein-A (PAPP-A) (0.6 vs. 0.9; P < 0.001) and free β-human chorionic gonadotropin (β-hCG) (0.9 vs. 1.1; P = 0.001) in the first trimester; median values of α-fetoprotein (AFP) (0.7 vs. 1.1; P = 0.027), unconjugated estriol 3 (uE3) (0.9 vs. 1.1; P < 0.001), and hCG (0.7 vs. 1.2; P < 0.001) in the second trimester were significantly lower with respect to control pregnancies. Multivariate analysis revealed that low uE3 and hCG levels were independently associated with APO. Conclusion: Pregnant women with hereditary thrombophilias, all of whom were treated with LMWH, had decreased levels of all first and second trimester serum markers. In addition, levels of hCG and uE3 in the second trimester could independently predict placenta-related disorders and adverse outcomes in these patients.     

Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia

Background: An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation.

Objective: To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n?=?20), and their controls matched for parity, and maternal and gestational age.

Method: Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay.

Results: Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9?pg/mL, artery and vein, respectively, p?0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0?±?298.4 versus 690.3?±?401.9 mIU/L, artery and vein, respectively, p?<?0.05), and free β-hCG (mean: 33.9?±?4.3 versus 17.2?±?4.0 and 30.1?±?5.2 versus 13.7?±?3.3?ng/mL, artery, and vein respectively, p?<?0.05).

Conclusion: Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.     

First trimester maternal serum analytes and second trimester uterine artery Doppler in the prediction of preeclampsia and fetal growth restriction

Objective

This study aimed to determine whether pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG), a disintegrin and metalloprotease 12 (ADAM12), and placenta protein 13 (PP13) in the first trimester, and uterine artery Doppler (UAD) in the second trimester, predict preeclampsia and fetal growth restriction (FGR).

Maternal Serum Human Placental Growth Hormone (hPGH) at 11 to 13 Weeks of Gestation in Preeclampsia

Objective. Human placental growth hormone (hPGH) is produced by human placenta and plays a central role in the maternal metabolic adjustments to pregnancy. The objective of this study was to investigate the maternal serum concentration of hPGH at 11–13 weeks of gestation in pregnancies that subsequently developed preeclampsia (PE), and to examine the possible association with uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A). Methods. The maternal serum concentration of hPGH at 11–13 weeks was measured in a case–control study from 60 cases that developed PE and 120 unaffected controls. The measured hPGH concentration was converted into a multiple of the expected median (MoM) in unaffected pregnancies. Regression analysis was used to determine the significance of association between hPGH MoM with uterine artery PI MoM and PAPP-A MoM. Results. In the pregnancies that subsequently developed PE the median serum hPGH concentration was not significantly different from that in the unaffected group (0.92 versus 1.00 MoM), whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no significant association between serum hPGH MoM and gestational age at delivery, uterine artery PI MoM, or serum PAPP-A MoM. Conclusion. The finding that in the PE group serum hPGH level during the first trimester is normal suggests that it is unlikely that this hormone plays a role in the pathogenesis of PE.     

The impact of assisted reproductive technology on the association between first-trimester pregnancy-associated plasma protein a and human chorionic gonadotropin and adverse pregnancy outcomes

We evaluated the impact of assisted reproductive technology (ART) on the association between first-trimester pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (β-hCG) and adverse pregnancy outcomes. PAPP-A and β-hCG levels were obtained between 11 and 13 (6)/ (7) weeks' gestation and converted to multiples of the median (MoM). MoM < 5th percentile was defined as low PAPP-A or β-hCG and those > 90th percentile as high. Adverse outcomes included small-for-gestational-age (SGA) infants, preeclampsia, pregnancy loss, and preterm delivery (PTD). Univariate and multivariate analyses were used to estimate the association. Of 4000 women meeting the inclusion criteria, 265 (7.6%) pregnancies were conceived by ART. ART pregnancies with low PAPP-A had a higher risk of having an SGA infant (odds ratio [OR] = 4.1, 95% confidence interval [CI] 1.2, 14.0) or PTD < 32 weeks (OR = 5.3, 95% CI 1.5, 18.6) compared with non-ART pregnancies with low PAPP-A (OR = 2.8, 95% CI 1.7, 4.7; OR = 3.9, 95% CI 2.1, 7.0, respectively). High PAPP-A was associated with pregnancy loss (OR = 6.1, 95% CI 1.1, 33.7) in ART pregnancies. Low β-hCG was associated with increased risk for PTD only in ART pregnancies (OR = 8.3, 95% CI 1.9, 35.9) for PTD < 37 weeks (OR 6.1, 95% CI 1.6, 23.0) for PTD < 35 weeks and (OR = 10.8, 95% CI 2.7, 43.7) for PTD < 32 weeks. High β-hCG was associated with increased risk for SGA (OR = 1.6, 95% CI 1.0, 2.5) and PTD < 37 weeks (OR = 1.4, 95% CI 1.0, 1.9) in non-ART pregnancies. The association between PAPP-A and β-hCG with adverse pregnancy outcomes is influenced by the mode of conception.     

Circulating levels of pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotrophin (hCG) in intrauterine and extrauterine pregnancies

Summary. Pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotrophin (hCG) have been measured in the plasma of pregnant and non-pregnant women attending the outpatient clinic for suspicion of pregnancy. The plasma concentrations obtained were grouped into intrauterine or extrauterine pregnancies and compared with values obtained in non-pregnant patients with similar periods of amenorrhoea. Patients with ectopic pregnancies had slightly lower PAPP-A levels and significantly lower hCG concentrations than those in women with normal intrauterine pregnancies. Non-pregnant women had very low hCG and PAPP-A levels compared with those in pregnant patients. These data suggest that in patients with extrauterine pregnancies the poorly sustained ectopic trophoblast is unable to produce normal concentrations of hCG and probably PAPP-A and that the slightly diminished levels of PAPP-A in ectopic pregnancies might be derived from a decidual production.     

Differential expression of human placental PAPP-A2 over gestation and in preeclampsia

IntroductionPregnancy Associated Plasma Protein A2 (PAPP-A2) is a pregnancy related insulin-like growth factor binding protein-5 (IGFBP-5) protease, known to be elevated in preeclampsia. As the insulin-like growth factors are important in human implantation and placentation, we sought to determine the expression pattern of PAPP-A2 over human gestation in normal and preeclamptic pregnancies to evaluate its role in placental development and the pathogenesis of preeclampsia.MethodsPlacental basal plate and chorionic villi samples, maternal and fetal cord blood sera were obtained from preeclamptic and control pregnancies. Formalin-fixed tissue sections from across gestation were stained for cytokeratin-7, HLA-G, and PAPP-A2. PAPP-A2 immunoblot analysis was also performed on protein lysates and sera.ResultsPAPP-A2 expression is predominately expressed by differentiated trophoblasts and fetal endothelium. Chorionic villi show strong expression in the first trimester, followed by a progressive decrease in the second trimester, which returns in the third trimester. PAPP-A2 expression is not impacted by labor. PAPP-A2 is increased in the basal plate, chorionic villi and maternal sera in preeclampsia compared to controls, but is not detectable in cord blood.DiscussionPAPP-A2 is differentially expressed in different trophoblast populations and shows strong down regulation in the mid second trimester in chorionic villous samples. Both maternal sera and placental tissue from pregnancies complicated by preeclampsia show increased levels of PAPP-A2. PAPP-A2 levels are not altered by labor. Additionally, PAPP-A2 cannot be detected in cord blood demonstrating that the alterations in maternal and placental PAPP-A2 are not recapitulated in the fetal circulation.     

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

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

Maternal serum levels of placental proteins after in vitro fertilisation and their implications for prenatal screening

OBJECTIVES: To determine whether the serum levels of pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific beta(1)-glycoprotein (SP1), placental lactogen (hPL) and human chorionic gonadotrophin (hCG) are different in pregnancies obtained after in vitro fertilisation (IVF) and embryo transfer (ET) in comparison to spontaneous pregnancies. Assessment of the need to establish normal medians for biochemical trisomy screening in IVF pregnancies. METHODS: The population comprised 96 IVF-ET pregnancies, of which 79 came from fresh gonadotrophin-stimulated cycles and 17 from embryo transfers without gonadotrophin stimulation (natural cycle IVF, frozen embryo transfers), and 156 spontaneous pregnancies. A single blood sample was obtained between 7 + 0 and 16 + 3 weeks. PAPP-A, SP1, hPL and hCG were quantified and the levels compared between gonadotrophin-stimulated IVF, steroid-only- or non-stimulated IVF, and controls with respect to gestational age using non-parametric statistical analysis. RESULTS: PAPP-A and hPL levels were reduced after stimulated IVF in early gestation (before 10 pregnancy weeks); SP1 followed the same trend without reaching statistical significance. hCG tended to be increased after IVF treatment including non-gonadotrophin-stimulation cycles, and also beyond 10 pregnancy weeks. CONCLUSION: Reduced PAPP-A with increased hCG yields an increased risk in screening for foetal trisomy 21. We confirm recently published observations but do not recommend the establishment of normal medians for IVF pregnancies since the extent of the deviations is varying according to the different stimulation protocols and dosages of gonadotrophins used.     

First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications

Objective To examine the value of first trimester maternal serum free β human chorionic gonadotrophin (β hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications.
Design Screening study.
Setting Antenatal clinics.
Population Singleton pregnancies at 10–14 weeks of gestation.
Methods Maternal serum free β hCG and PAPP-A were measured at 10–14 weeks of gestation in 5584 singleton pregnancies. In the 5297 (94.9%) pregnancies with complete follow up free β hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes.
Results Maternal serum PAPP-A increased and β hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free β hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes.
Conclusion Low maternal serum PAPP-A or β hCG at 10–14 weeks of gestation are associated with subsequent development of pregnancy complications.     

Pregancy-specific and pregnancy-associated proteins in threatened abortion

Pregnancy sera (390) were taken between the 5th and 16th weeks of gestation, from subjects whose pregnancies were uneventful throughout the entire gestation period. In-house curves of first-trimester normal values (10th, 50th, 90th percentile) were established for human chorionic gonadotropin (hCG), human placental lactogen (hPL), pregnancy-specific β₁-glycoprotein (SP-1), pregnancy-associated plasma protein A (PAPP-A), and pregnancy-associated α₂-glyco-protein (α₂-PAG) after the measurement of these proteins in the sera by immunoassay.

Eighty sera from patients with threatened abortion were also obtained and the placental proteins mentioned above were determined. Values falling below the 10th percentile of the normal population were classified as positive (i.e., pathological) results; the others were considered negative. Based on the outcome of the pregnancy, the results were grouped into true positives (low value and lost pregnancy), false positives (low value and ongoing pregnancy), true negatives, and false negatives. The sensitivity, specificity, and the positive predictive value of each protein as an indicator for abortion were calculated.

In terms of specificity hCG and SP-1 were good, whilst PAPP-A and hCG showed the highest sensitivity. The best predictive values were obtained from SP-1 and hCG. The results show that PAPP-A and SP-1 perform satisfactorily but that none of these proteins significantly improves on hCG.     

2D-ultrasound and endocrinologic evaluation of placentation in early pregnancy and its relationship to fetal birthweight in normal pregnancies and pre-eclampsia

Objectives

To study the relationships between 2D ultrasound measurements of placentation and maternal serum (MS) levels of PAPP-A, inhibin A and fβhCG in early pregnancy and subsequent fetal growth in pregnancies with a normal and abnormal outcome.

Study design

Prospective population-based cohort study of 301 pregnancies with a normal outcome, 18 with a pregnancy complicated by pre-term delivery (PTD) and 14 with subsequent pre-eclampsia (PE).

Main outcome measures

Basal placental surface area, placental thickness, ellipsivity and volume; MS PAPP-A and fβhCG at 11–13 + 6 weeks, MS inhibin A at 15–22 weeks and birthweight centile at delivery.

Results

In the normal group, the basal surface area showed a significantly (P < 0.001) positive correlation with placental thickness and placental ellipsivity. With the exception of placental ellipsivity, all other placental ultrasound parameters were significantly related with birthweight centile. Inhibin A showed a significant (P < 0.005) correlation with birthweight centiles. The basal plate surface area and MS PAPP-A were significantly (P < 0.01 and P < 0.001, respectively) lower and MS inhibin A significantly (P < 0.01) higher in PE than in controls. No changes were found in pregnancies complicated by PTD.

Conclusion

The basal plate surface area at 11–14 weeks reflects indirectly normal and abnormal placentation and development of the definitive placenta. Combined with MS PAPP-A and/or inhibin A levels this parameter could be useful in identifying from the end of the first trimester, pregnancies subsequently complicated with PE.     

First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction

Objective

We test the hypothesis that first-trimester serum analytes, 4-D power Doppler placental vascular indices and uterine artery Doppler (UAD) predicts abnormal placental morphometry in pregnancies with preeclampsia (PE) and fetal growth restriction (FGR).

Study design

Maternal serum analytes (PAPP-A, hCG, ADAM12s, and PP13), bilateral UADs, and placental vascular indices were measured at 11-14 weeks in a nested-case control study within a prospective cohort of women followed from the first-trimester to delivery. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained from 4-D power Doppler histograms. Serum analytes were measured using immunofluorometric assays and values converted to multiples of the median (MoM) for gestational age. Morphometric analysis was performed on placentas from pregnancies complicated by PE (n = 13), gestational hypertension (HBP, n = 7) and FGR (defined as fetal weight <10th percentile with abnormal umbilical artery Doppler: n = 7); and 20 uncomplicated pregnancies. Two pregnancies had both FGR and PE. Each placenta was weighed and random samples taken, and fixed in formalin within 1 h of delivery. Hematoxylin & Eosin stained slides were analyzed by design-based stereology to quantify linear dimensions, surface areas and volumes of placental components. Paired t-test and ANOVA with adjustments for multiple comparisons were used.

Results

The surface areas of terminal and intermediate villi as well as the volume of terminal villi were significantly smaller in placentas from pregnancies complicated by FGR and PE. Compared with the control group the mean PAPP-A (MoM) was lower in the pregnancies with abnormal placenta morphometry (1.1 ± 0.5 versus 0.7 ± 0.5, P = 0.03). The morphometric indices were lower in those pregnancies with low PAPP-A and IUGR compared with preeclampsia.

Conclusion

First-trimester PAPP-A levels are associated with abnormal placental morphometry at delivery in pregnancies with PE and IUGR. These findings may explain the association between adverse pregnancy outcomes and first-trimester PAPP-A.     

Genetic Variation of Myeloperoxidase Gene Contributes to Preeclampsia: A Preliminary Association Study in Turkish Population

Objective. To examine MPO gene polymorphisms of women with preeclampsia in Turkish population. Methods. Sixty-one preeclamptic and 61 normotensive women without history of preeclampsia in earlier pregnancies were enrolled in this prospective controlled study. MPO mutations were characterized by PCR-RFLP method. Results. We demonstrated a significant difference in patients with preeclampsia in terms of genotype frequency. Heterozygous carriers of??463A among preeclamptic pregnancies were significantly frequent, whereas rare A/A homozygotes failed to differ from controls. Conclusion. The??463G/A polymorphism of leukocyte MPO could be an intriguing susceptibility factor that modulates an individual's risk of preeclampsia in Turkish population.