Pregnancy-associated Plasma protein-A Multiples Of Median Research Articles

Clinical value of prenatal screening markers in early pregnancy combined with perinatal characteristics to predict fetal growth restriction.

Due to the incomplete standardization of the etiology and diagnostic criteria for fetal growth restriction (FGR), there has been uncertainty in the early prediction of FGR. The comprehensive estimation of FGR was mainly based on various factors, such as maternal characteristics and medical history, nuchal translucency (NT), and serum biochemical markers [pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (free β-hCG)]. Herein, we performed a retrospective cohort study to investigate the correlation and diagnostic value of maternal markers such as PAPP-A, free β-hCG, and NT in the first trimester with maternal characteristics, so as to provide theoretical basis for perinatal care and the application of low-dose aspirin. A retrospective cohort study was conducted to analyze the data of an FGR group and a non-FGR group. Chi-square test and Mann-Whitney U test were used for univariate analysis of qualitative or quantitative data, respectively. Modified Poisson regression calculated the relative risk (RR) and 95% confidence interval (CI) of perinatal variables; P<0.05 was considered statistically significant. The multiple of median (MoM) of PAPP-A level and NT in the FGR group were lower than those of the non-FGR group [0.63 (0.12-2.08) vs. 1.01 (0.28-2.41) MoM, 1.30 (0.80-2.07) vs. 1.40 (0.80-2.20) cm, P<0.05]. The weight, score, and length of newborns in the FGR group were lower than those in the non-FGR group (all P<0.001). Modified Poisson regression analysis showed that gestational hypertension (GH) [RR =1.836 (95% CI: 1.188-2.836)], oligohydramnios [1.420 (95% CI: 1.022-1.973)], premature rupture of membranes (PROM) [0.641 (95% CI: 0.425-0.969)], female infant [1.539 (95% CI: 1.098-2.157)], low infant length [5.700 (95% CI: 3.416-9.509)], low birth weight [1.609 (95% CI: 1.012-2.559), and increased PAPP-A MoM [0.533 (95% CI: 0.369-0.769)] were associated with FGR. The cut-off value of PAPP-A + free β-hCG + NT for predicting FGR was 0.190, with a sensitivity of 0.547 and a specificity of 0.778. Early screening markers combined with perinatal characteristics have better diagnostic value in predicting FGR and provide a scientific basis for the clinical use of low-dose aspirin to prevent FGR.

The predictive value of first trimester maternal serum pregnancy-associated plasma protein-a (papp-a) level in predicting gestational diabetes mellitus

Aims: The aim of this study is to evaluate the predictive value of first trimester biochemical markers in the subsequent development of gestational diabetes mellitus. Methods: Data were retrospectively collected from the file records of 361 pregnant patients, who were admitted to the 1st Obstetrics and Gynecology Clinic at Sisli Etfal Education and Training Hospital for first trimester prenatal screening test between 11-14 weeks of their gestation and who later had undergone 50 gram glucose challenge test at 24-28 weeks of their gestation, between November 2007 and February 2011. Age, patient weight, Crown rump length (CRL), gestational week, Pregnancy-Associated Plasma Protein-A (PAPP-A) concentration, PAPP-A multiple of median (MoM) value, Beta-human koryonik gonadotropin (B-HCG) concentration, B-HCG MoM value, 50 and 100 g oral glucose challange test result were recorded from the files. Gestational diabetes was diagnosed according to National Diabates Data Grup cutt-off values and criteria. The association between first trimester biochemical markers and subsequent development of gestational diabetes was evaluated. Results: In this study low PAPP-A and/or HCG MoM values and increased Nuchal translucency (NT) MoM values were found to be statistically significant for subsequent development of gestational diabetes. Conclusion: GDM is an important health problem that carries many risks of complications for both mother and fetus. Pregnant women with GDM may have high blood sugar levels before diagnosis at 24 weeks of gestation, so fetal growth may be negatively affected by maternal hyperglycemia. Use of first trimester screening maternal serum biomarkers may lead to early diagnosis of GDM and interventions to improve maternal and fetal outcomes.

Early Prediction of Small for Gestational Age (SGA): The Predictive Role of Pregnancy Associated Plasma Protein-A

Introduction: Small for Gestational Age (SGA) is a compelling obstetric adversity with multiple consequences. Early diagnosis, although a challenge, can help blunt the adverse effects. One of the markers is Pregnancy Associated Plasma Protein-A (PAPP-A) which can be an early predictor of SGA. Aim: To find the association of low levels of pregnancy associated plasma protein-A with small for gestational age. Materials and methods: This prospective observational study was conducted in the Department of Obstetrics and Gynaecology at All India Institute of Medical Sciences, Raipur, Chhattisgarh, India, between June 2018 and September 2019. The demographic profile, PAPP-A Multiples of Median (MoM) levels, complications in pregnancy and birth outcome data of a total of 203 women were noted. For analysis of descriptive and categorical data, IBM Statistical Package for the Social Sciences (SPSS) statistical software version 23.0 was used. Shapiro-Wilk and KolmogorovSmirnov tests were performed to assess normality of distribution. Qualitative data were analysed by Chi-square test and categorical data, by Mann-Whitney’s U test. Results: The prevalence of SGA was 18.2%, out of which PAPP-A MoM levels were ≤0.49 in 59.4%. The association between PAPP-A levels and SGA was statistically significant (p-value=0.03) with unadjusted odds ratio of 8.27 (95%CI, 3.78-18.08). Simple logistic regression showed an inverse relationship of PAPP-A with SGA. At the cut-off of ≤0.49 considered in the study, sensitivity was 86.7%, specificity was 54.1%, positive predictive value was 29.5% and negative predictive value was 94.8%. Positive likelihood ratio was 1.88 and negative likelihood ratio was 0.24 and the diagnostic accuracy was found to be 59.9%. Conclusion: An inverse relationship between levels of PAPP-A MoM (≤0.49) and SGA was found in the study. Low levels of PAPP-A MoM can be a useful early predictor of SGA.

Antenatal fetal death in multiple pregnancy: is early prediction possible?

Introduction. Perinatal mortality in multiple pregnancies increases by 8–10 times compared to singletons. Stillbirth is a significant part of all complications of multiple pregnancies. Although the incidence of perinatal mortality in multiple pregnancies has decreased consistently compared to extremely high rates in the past, it remains relatively high, despite significant positive changes in the management of such pregnancies. Aim: to assess the diagnostic potential of the first trimester's biochemical screening in multiple pregnancies for predicting antenatal fetal death. Materials and Methods. As part of a retrospective study, a cohort of twin pregnancies after in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or spontaneous conception underwent screening of the first trimester at 11+0–13+6 weeks of gestation as recommended by the Fetal Medicine Foundation. Determination of pregnancy-associated plasma protein-A (PAPP-A) in blood serum with subsequent calculation of the relative PAPP-A MoM (multiples of median) – a multiple of the median (an indicator of how much the individual test result deviates from the reference values) was performed. Results. Prenatal screening and outcomes of 302 multiple pregnancies showed that with PAPP-A MoM &lt; 0.5, antenatal fetal death occurred with a frequency of 42.86 % (6/14), with PAPP-A MoM within the reference values – In 12.67 % (28/221), with PAPP-A MoM &gt; 2.0 – in 6.7 % (2/30). Differences between patients with PAPP-A MoM &lt; 0.5 and PAPP-A MoM within the reference values, as well as PAPP-A MoM &lt; 0.5 and PAPP-A MoM &gt; 2.0 were statistically significant (p = 0.002 and p = 0.004, respectively). No differences were detected between spontaneous and assisted reproductive technology (ART) pregnancies. Conclusion. In women with multiple pregnancies resulting from ART or spontaneous, PAPP-A MoM values below the reference interval (&lt; 0.5) in the first trimester are associated with an increased risk of antenatal fetal death.

Maternal Pregnancy Associated Plasma Protein-A Levels in Late First Trimester as a Predictor of Miscarriage- A Cross-sectional Study

Indroduction: Miscarriage is the most common complication of pregnancy. Defective implantation is one of the common causes of miscarriage. Pregnancy Associated Plasma Protein-A (PAPP-A) is secreted from syncytiotrophoblast and it enables trophoblast invasion. Few studies have shown association of PAPP-A with miscarriage. However, there is limited data available to establish the role of PAPP-A as a predictive marker of miscarriage, especially in Indian population. Aim: To determine the potential of maternal PAPP-A level estimation in asymptomatic women in late first trimester (10-13 weeks) with viable foetus in predicting subsequent miscarriage. Materials and Methods: This was an observational, cross-sectional study conducted from November 2016 to April 2018 at University College of Medical Science and Guru Teg Bahadur Hospital, Delhi, India. Asymptomatic pregnant women (N=500) at 10-13 weeks of gestation were recruited from an antenatal clinic after confirmation of foetal viability. A 2 mL of blood sample was collected and serum PAPP-A level was measured. Independent t-test and Chi-square test was used to compare continuous data and Mann-Whitney U test was used to compare PAPP-A Multiple of Median (MOM). Logistic regression was used to estimate risk of miscarriage. Results: Out of 500 participants, 9 were lost to follow-up. From remaining N=491, 32 (6.5%) women had a miscarriage. PAPP-A levels were significantly decreased in miscarriage group compared to ongoing pregnancy group with median MOM 0.116 (0.080-0.17) and 1.25 (0.665-3.249) respectively (p-value &lt;0.001). PAPP-A MOM value of ≤10th percentile sensitivity and specificity of detection of miscarriage was 81.25% and 94.98% and at ≤5th percentile sensitivity and specificity was 40.62% and 97.82%, respectively. Lower the percentile cut-off of serum PAPP-A value, higher was the specificity and positive predictive value for prediction of miscarriage. By applying logistic regression we found that if PAPP-A MOM decreases by 1 unit the chances of miscarriage increased by 1.2 times. By this model 63.2% of cases could be explained (Nagelkerke R Square=0.632). For prediction of pregnancies likely to miscarry, the area under Receiver Operator Characteristic (ROC) curve (95% CI) was 0.969 (0.955-0.983). Conclusion: Low serum PAPP-A levels from asymptomatic women in late 1st trimester is a good predictive marker of miscarriage.

The significance of maternal blood pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (β-hCG) levels for the risk assessment of fetal trisomy 18 during the first prenatal testing between 11 and 13+6 weeks of pregnancy.

The aim of the study was to evaluate the significance of the maternal blood level of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (β-hCG), to estimate the risk of fetal trisomy 18 and their correlation with the assessment of nuchal translucency (NT) during the first prenatal testing. Examinations of 93 pregnant women between 11 and 13+6 weeks of pregnancy were conducted, which included determination of β-hCG and PAPP-A concentrations in the maternal serum and ultrasound assessment of fetal nuchal translucency. Concentrations of biochemical parameters were expressed as multiples of median (MoM) for the appropriate gestational age. The risk assessment of trisomy 18 was analyzed using Astraia software. Pregnant women with a high (≥ 1:300) risk of trisomy 18 were offered a genetic amniocentesis with an examination of fetal karyotype. Twenty cases were healthy and 23 with trisomy 18. PAPP-A and β-hCG MoM values < 0.3 were found in 61% cases of fetal trisomy 18. In 26% of cases, PAPP-A and β-hCG MoM values < 0.2 were NT-independent risk factors for trisomy 18. There were no significant differences between groups with normal fetal karyotype (40%) and trisomy 18 (35%) in PAPP-A and β-hCG MoM 0.2-0.5 range. Maternal free β-hCG MoM was found to change parallelly to fetal NT widening in case of trisomy 18 diagnosis. Maternal β-hCG and PAPP-A MoM results presented less then 0.2 might be used independently of NT widening in fetus for trisomy 18 risk evaluation. Above 0.2 for PAPP-A and β-hCG MoMs, fetal NT measurement was an requirment.

First trimester prenatal screening in multiple pregnancies. Part II: serum proteins PAPP-A and β-hCG as markers of adverse pregnancy outcomes

Aim: to evaluate the ability of serum biochemical markers in pregnant woman - PAPP-A (pregnancy-associated plasma protein-A) and β-hCG (the в-subunit of human chorionic gonadotropin) studied in the first trimester (11 +0 -13 +6 ) during combined prenatal screening to predict adverse perinatal outcomes of multiple pregnancy that occurred spontaneously and as a result of in vitro fertilization (IVF). Materials and methods . The main group consisted from 65 women with pregnancy occurred as a result of IVF; comparison group included 56 women with spontaneous pregnancy. All pregnancies were multiple and their outcomes were known. Serum PAPP-A and β-hCG levels were measured in the first trimester. The results were expressed in absolute values and in MoM (multiples of median). Subgroups were compared with mono- and dichorionic pregnancies, complicated and uncomplicated pregnancies, distributed according to MoM index: within the reference values (0.5-2.0), below or above the reference values. Results . PAPP-A MoM values in the spontaneous pregnancy group were 1.12 [0.8; 1.57], in the IVF group - 1.35 [1.11; 1.72] (p = 0.01). In subgroup of low PAPP-A MoM antenatal fetal death occurred in 50 %, in subgroup of normal PAPP-A MoM - in 14.58 %, in subgroup of high PAPP-A MoM - in 5.88 % (p = 0.011). In addition, a positive correlation was found between serum PAPP-A level and time of fetal death (r s = 0.564; p = 0.036). Low PAPP-A MoM values were associated with 50 % fetal mortality, 75 % of them were attributable to pregnancy as a result of IVF. Conclusion . Identification of adverse outcomes in multiple pregnancies is still a difficult task, but evaluation of serum biochemical markers during the first trimester screening can help in early diagnosis of necessity and extent of timely prophylaxis.

The utility of pregnancy associated plasma protein-A MoM values in prediction of term respiratory distress syndrome

This study aimed to investigate if the pregnancy associated plasma Protein-A (PAPP-A) multiples of median (MoM) levels could be used as a marker for the early prediction of RDS. The present study was designed with data gathered from 1773 patients who were referred to our institution for first trimester fetal chromosomal anomaly screening. First trimester PAPP-A MoM values and postnatal RDS occurrences in these pregnancies were retrospectively analysed. Of the 1773 neonates that were included in the study, 28 were delivered at or beyond 37 weeks, and 42 were delivered less than 37 weeks of gestation. In the group of neonates at or beyond 37 weeks, the cut-off value for RDS prediction was determined as 1.02. For this cut-off value, sensitivity was 72.41% and specificity was 91.84%. The area under curve (AUC) was determined to be statistically significant (p < .01). In conclusion, it was determined that in neonates that were delivered at or beyond 37 weeks of gestation, RDS occurrence could be predicted at a significant rate by utilising PAPP-A MoM values.IMPACT STATEMENTWhat is already known on this subject? Respiratory distress syndrome (RDS) is one of the major global healthcare problems, and continues to effect newborns despite the improvements in diagnosis and treatments of the disease. Studies have shown that pregnancy associated plasma protein-A (PAPP-A) has a critical role in cellular proliferation and differentiation, and it is closely associated with many physiological and pathological processes via regulation of local insulin like growth factor (IGF) concentrations. In majority of the past studies in the literature regarding PAPP-A values in pregnancies, the association between low values of PAPP-A MoM and maternal-fetal complications were investigated.What do the results of this study add? This study retrospectively examines the PAPP-A MoM levels and the occurence of RDS. In neonates that were delivered at or beyond 37 weeks of gestation, RDS occurrence could be predicted at a significant rate by utilising PAPP-A MoM values which was measured at the first trimester fetal anomaly screening test.What are the implications of these findings for clinical practice and/or further research? In the light of these findings, in order to reduce RDS related neonatal morbidity and mortality, pregnancies with PAPP-A MoM values greater than 1.02 at the first trimester fetal anomaly screening should be more closely followed up and a higher rate of suspicion should be kept for RDS occurrence.

The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications.

The aim of this study was to determine if the levels of biochemical aneuploidy markers in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to verify if biochemical markers could predict pregnancy outcome in IVF/ICSI gestations. This was a prospective observational study performed in a group of 551 patients who underwent a combined first trimester prenatal screening (ultrasound scan and serum markers). All patients were divided into two groups according to the mode of conception: IVF/ICSI pregnancies (study group) and spontaneous conceptions (control group). The concentrations of first trimester biochemical markers were presented as multiples of median (MoM) and were compared between the study and control groups. Analysed pregnancy complications included: preterm delivery (PTD), small for gestational age (SGA), gestational hypertension (GH), preeclampsia (PE) and gestational diabetes (GDM). The analysis was performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with complete data regarding obstetric outcome. There were no significant differences in the concentrations of biochemical markers between the analysed groups. Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive than in normotensive patients, although the difference was not significant. Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed in 18 (9.8%) and 25 delivered preterm (13.6%). The trend for lower PAPP-A MoM was visible in all affected patients, although the results did not reach statistical significance. The first trimester biochemical markers in assisted reproduction technique (ART) pregnancies do not seem to have additional effect on predicting the risk of pregnancy complications.

Could first- and second-trimester biochemical markers for Down syndrome have a role in predicting intrahepatic cholestasis of pregnancy?

IntroductionThe aim of this study is to compare first- and second-trimester Down syndrome biochemical screening markers in intrahepatic cholestasis of pregnancy (ICP) and normal pregnancies.Material and methodsThis observational case-control study was conducted at Health Sciences University Zeynep Kamil Maternity and Children’s Health Training and Research Hospital and the Department of Obstetrics and Gynecology at Erciyes University Medical Faculty during 2016–2017. The study included 165 patients, and consisted of 62 women who had been diagnosed with ICP (the ICP-diagnosed group) and 103 healthy pregnant women (the control group). First-trimester free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A) and second-trimester total β-hCG, estriol (E3), α-fetoprotein (AFP), and inhibin A levels were compared between the two groups.ResultsThe mean patient age was 28.67 ±5.96 years, with no significant difference between the groups (p > 0.05). Average PAPP-A levels were significantly lower in the ICP-diagnosed group (p < 0.001). When the cut-off value for PAPP-A was taken as ≤ 0.93 multiple of median (MoM), the sensitivity and specificity values for ICP were 73.8% and 56.3%, respectively (95% CI, AUC ± SE: 0.663 ±0.042).ConclusionsThe decrease in PAPP-A MoM value indicates an increase in the risk of developing ICP, while changes in other markers were not sufficient to predict ICP.

Pregnancy-Associated Plasma Protein A Levels in Late First Trimester Pregnancies with Small-for-Gestational Age Neonates: A Prospective Case-Control Study.

We aimed to investigate the association of pregnancy associated plasma protein A (PAPP-A) levels in late first trimester with small for gestational age (SGA) neonates and adverse pregnancy outcomes in a low-income setting. The inclusion criteria were late first trimester (11-13+6weeks) women with singleton and non-anomalous pregnancy. Enrolled participants were sampled for PAPP-A and prospectively followed up for delivery outcome and antenatal complications. A multiple of median (MoM) was calculated and statistically compared between groups. Out of total 284 subjects, 14.54% delivered SGA babies and formed cases (Group A), 66.5% delivered appropriate for gestational age (AGA) neonates with uneventful antenatal period (controls, Group B), and 19.3% were AGA group with adverse pregnancy complications (Group C). The late first trimester median PAPP-A MoM was significantly lower (0.61) in Group A compared to Group B (1.47). Using receiver operating characteristic (ROC) curve for PAPP-A MoM, optimal cutoff value was found at 0.45 MoM, with positive predictive value of 56.2%, specificity of 92.6% and sensitivity of 45%. The median interquartile range (IQR) of PAPP-A MoM value in Group C in comparison with Group B was significantly lower except for abruption. At PAPP-A MoM cutoff value <1, <0.8, <0.6 and <0.4, the odds ratio for adverse pregnancy outcome was 8.30, 7.29, 10.97 and 10.60, respectively, indicating an inverse relationship. With 0.45 MoM cutoff of PAPP-A, the detection rate, specificity and positive predictive value for SGA were 45, 92.6 and 56.2%, respectively. As PAPP-A MoM values decreased, the odds ratio of having adverse pregnancy outcomes increased.

Does Endometriosis Affect PAPP-A Concentration in First Trimester Fetal Screening Test?

Objective Pregnancy-associated plasma protein A (PAPP-A) is a macromolecular glycoprotein. The peritoneal fluid of women affected by endometriosis shows a significant increase of PAPP-A levels. Given the important role of PAPP-A in first trimester screening test, we wondered if its presence in the peritoneal fluid of women with endometriosis could affect biochemical parameters of the test performed during pregnancy. Methods A prospective study enrolled 78 women with singleton pregnancy who performed combined test between 11 + 0 and 13 + 6 weeks of gestation: 25 women with previous histological diagnosis of endometriosis and 53 women without. All patients were sampled to determine PAPP-A concentrations. Serum levels of PAPP-A were expressed in UI/L and in MoM (multiples of median). The two groups – endometriosis women and non-endometriosis women – were compared in order to find a possible different concentration of serum PAPP-A. Results We found an increased concentration of both PAPP-A UI/L and PAPP-A MoM in deep endometriosis patients versus ovarian endometriosis with significant difference in PAPP-A MoM (p = 0.018). We also found a significant association between the stage of the disease and PAPP-A UI/L and MoM levels (PAPP-A UI/L p = 0.05, PAPP-A MoM p = 0.01). Conclusions Women with deep endometriosis show increased serum PAPP-A concentrations compared to women with ovarian endometriosis. Likewise, women with moderate or severe stage of the disease show increased serum PAPP-A concentrations compared to women with minimum or mild disease. This increase could affect first trimester aneuploidy screening test and endometriosis could represent a confounding factor in the calculation of aneuploidy risk.

First trimester screening for other trisomies than trisomy 21, 18, and 13.

The objective of the study was to evaluate the performance of first trimester combined screening in cases of placental/fetal, mosaic or non-mosaic, autosomal trisomy other than trisomy 21, 18, or 13, and in cases of aneuploidy for a marker chromosome with focus on biochemical markers. We identified 66 cases in three large databases including 357 675 pregnancies from October 2003 to January 2014. Seventy-seven percent of the 66 cases were screened positive at the combined first trimester screening (cFTS) for trisomy 21 or trisomy 18 or 13. The multiple of median (MoM) of Pregnancy Associated plasma protein A (PAPP-A) of the different aneuploidy groups ranged from 0.2 to 0.5 MoM, whereas the MoM of maternal serum free - β - human chorionic gonadotropin (FβhCG) was approximately 1.0 MoM. The exceptions being 0.2 MoM for cases involving chromosome 8 (n = 7) and 0.5 MoM for cases involving chromosome 9 (n = 3). The nuchal translucency MoM was approximately 1.0 MoM in all aneuploidy groups. The cFTS program for trisomy 21, 18, and 13 is also sensitive to a broad range of rare chromosomal trisomies and chromosomal mosaicisms, primarily because of a strong detection capacity of PAPP-A MoM.

First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia

BackgroundFirst trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia. This study tests the hypothesis that first trimester PAPP-A levels correlate with soluble fms-like tyrosine kinase-1 (sFlt-1) levels, an angiogenic marker associated with preeclampsia, throughout pregnancy.MethodssFlt-1 levels were measured longitudinally in 427 women with singleton pregnancies in all three trimesters. First trimester PAPP-A and PAPP-A Multiples of Median (MOM) were measured. Student’s T and Wilcoxon tests compared preeclamptic and normal pregnancies. A linear mixed model assessed the relationship between log PAPP-A and serial log sFlt-1 levels.ResultsPAPP-A and PAPP-A MOM levels were significantly lower in preeclamptic (n = 19), versus normal pregnancies (p = 0.02). Although mean third trimester sFlt-1 levels were significantly higher in preeclampsia (p = 0.002), first trimester sFlt-1 levels were lower in women who developed preeclampsia, compared with normal pregnancies (p = 0.03). PAPP-A levels correlated significantly with serial sFlt-1 levels. Importantly, low first trimester PAPP-A MOM predicted decreased odds of normal pregnancy (OR 0.2, p = 0.002).ConclusionsLow first trimester PAPP-A levels suggests increased future risk of preeclampsia and correlate with serial sFlt-1 levels throughout pregnancy. Furthermore, low first trimester PAPP-A status significantly predicted decreased odds of normal pregnancy.

Umbilical cord insertion into the lower segment of the uterus at 11 to 13 weeks' gestation is associated with maternal serum PAPP‐A

To evaluate whether the location of the placental cord insertion (CI) at 11 to 13 weeks' gestation affects the maternal serum pregnancy-associated plasma protein-A (PAPP-A). Cohort study was conducted in patients who underwent the first trimester screening including nuchal translucency and blood test. We additionally documented the CI site. The thickness of the placenta under the CI and the minimum distance on the uterine wall between the internal cervical os and the CI (Dis) were measured. The subjects were divided into two groups. Below the tenth percentile in multiples of median (MoM) of Dis were defined as cases in which CI was located on the lower uterine segment (low CI) and the others were defined as controls. A total of 117 subjects were analyzed. The thickness of the placenta (r = 0.237, p = 0.010) and Dis (r = 0.243, p = 0.008) was correlated with the crown-rump length (CRL). The maternal serum PAPP-A MoM in the low CI group was lower than in controls (0.76 ± 0.34 vs 1.16 ± 0.55; p = 0.009), whereas the other ultrasonographic measurements and maternal demographics were not different between the two groups. CI on the lower segment of the uterus is associated with low maternal serum PAPP-A MoM levels.

The relationship between first trimester fetal growth, pregnancy‐associated plasma protein A levels and birthweight

We sought to define the relationship between first trimester fetal growth, pregnancy-associated plasma protein A (PAPP-A) levels and birthweight. Two-hundred and one women with repeat first trimester crown-rump length (CRL) measurements were included. In 194, the first trimester PAPP-A value was known and in 169 there was complete data including birthweight. Fetal growth curves were derived using functional linear discriminant analysis (FLDA) and growth compared between those with < 10th percentile, 10th to 90th and > 90th percentile PAPP-A multiple of median (MoM) levels and birthweight percentiles. Median maternal age was 35 years, gestation at PAPP-A sampling and of first scan was 11 weeks. Median delivery gestation was 40 weeks and birthweight 3425 g. There was no association between first trimester fetal CRL growth and either PAPP-A MoM percentile or birthweight percentile. There was a significant positive correlation between PAPP-A MoM and birthweight percentile (p = 0.0004). First trimester fetal growth rate is not related to birthweight percentile or first trimester PAPP-A levels. Irrespective of gestation, a low PAPP-A is associated with delivery of a smaller baby, and a high PAPP-A with a larger baby.

First-trimester maternal serum levels of placental hormones are independent predictors of second-trimester fetal growth parameters

To determine whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of second-trimester fetal growth parameters. This was a cohort study over a 1-year period involving 594 Chinese women who underwent both first-trimester combined screening for Down syndrome and a routine second-trimester ultrasound examination. Maternal PAPP-A and fbeta-hCG levels (expressed in log(10) of multiples of median (MoM)), crown-rump length (CRL) (expressed in standardized Z-score (Z-CRL)), and maternal height and weight, were correlated with the Z-score of biparietal diameter (Z-BPD), femur length (Z-FL) and abdominal circumference (Z-AC) measured in the second trimester, using the Pearson test, followed by multiple regression analysis. Z-BPD, Z-FL and Z-AC were positively correlated with log(10) PAPP-A MoM, CRL and maternal height (all P < 0.05), while log(10) fbeta-hCG MoM was negatively correlated with Z-AC (P < 0.05). After controlling for the effects of CRL, maternal height and weight, log(10) PAPP-A MoM was found to be an independent positive predictor of Z-FL (r = 0.797, P < 0.001) and Z-AC (r = 0.305, P = 0.049), and log(10) fbeta-hCG MoM was an independent negative predictor of Z-FL (r = -0.381, P = 0.023) and Z-AC (r = -0.418, P = 0.002). Neither hormonal level was related to Z-BPD. First-trimester PAPP-A and fbeta-hCG are independent factors that influence subsequent fetal growth. PAPP-A level is positively correlated with FL and AC in the second trimester, while fbeta-hCG level is negatively correlated with them. However, BPD is not affected by either of the hormones.