Pregnancy-associated Plasma protein-A MoM Research Articles

First-trimester serum biomarkers in twin pregnancies and adverse obstetric outcomes–a single center cohort study

PurposeThis study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies.MethodsThis is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used.Results466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks.ConclusionA high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.

Combined first-trimester screening and invasive diagnostics for atypical chromosomal aberrations: Danish nationwide data on prenatal profiles and detection compared with NIPT.

To examine the prenatal profiles of pregnancies affected by an atypical chromosomal aberration, focusing on pathogenic copy number variants (pCNVs). Further, we wanted to quantify the performance of combined first-trimester screening (cFTS) and a second-trimester anomaly scan in detecting these conditions. Finally, we aimed to estimate the consequences of a policy of using non-invasive prenatal testing (NIPT) rather than invasive testing with chromosomal microarray (CMA) to manage pregnancies identified as high risk from cFTS. A retrospective review of the Danish fetal medicine database identified all pregnant women who had cFTS and a trisomy 21 risk-assessment between January 1, 2008, and December 31, 2018. Chromosomal aberrations diagnosed prenatally, postnatally, or from fetal tissue following pregnancy loss or termination of pregnancy (TOP) were identified. Chromosomal aberrations were grouped into one of six categories: 1) Triploidy; 2) Common trisomies (trisomies 21, 18, and 13); 3) Monosomy X; 4) Other sex chromosome aberrations (SCAs); 5) pCNVs; and 6) Rare autosomal trisomies (RATs) and mosaicisms. The prevalence of each aberration-category was stratified by the individual cFTS markers and risk estimate, and the size of each pCNV diagnosed from CMA was calculated. We included data on 565,708 pregnancies of which 3,982 were diagnosed with a fetal chromosomal aberration (0.70%). cFTS performed well in identifying triploidies (86%), monosomy X (92%), atypical SCAs (58%), and RATs and mosaicisms (70%). pCNVs comprised 28% (n=1,091) of the chromosomal aberrations diagnosed overall, and the prevalence increased during the study period with more prenatal chromosomal microarray analysis being performed. In pregnancies with maternal age <30 years, NT <95th percentile, PAPP-A MoM ≥ 1, or trisomy 21 risk ≥1 in 1000, the prevalence of pCNVs significantly exceeded the prevalence of trisomies 21, 18, and 13. Pregnancies affected by a pCNV had significantly increased nuchal translucency thickness (NT) and decreased maternal biomarkers pregnancy associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) compared with unaffected pregnancies. However, only 23% of these pregnancies screened positive from cFTS and 51% were not detected until after birth. Amongst high-risk pregnancies diagnosed with a chromosomal aberration, pCNVs comprised 14% and when other atypical aberrations were considered, conventional NIPT (screening for trisomies 21, 18, and 13, and monosomy X) would miss 28% of all pathogenic aberrations diagnosed following a high-risk cFTS result. Thus, 1 in 26 pregnancies at high-risk following cFTS would be affected by a chromosomal aberration despite a normal conventional NIPT result. In a contingent screening model with NIPT provided for the "intermediate" risk group (T21 risk of 1 in 100-300), 50% of the aberrations would be missed. In our cohort, 80% of the pCNVs diagnosed were <5Mb and therefore not detectable using current forms of "genome wide" NIPT. As a by-product to screening for trisomies 21, 18, and 13, most triploidies and the majority of atypical SCAs, RATs, and mosaicisms are detected before birth. However, only 23% of pCNVs are high-risk from cFTS and only half are diagnosed before birth. Replacing invasive testing with NIPT for high-risk pregnancies would substantially decrease the first-trimester detection of pathogenic chromosomal anomalies. This article is protected by copyright. All rights reserved.

Navigating Uncertain Waters: First-Trimester Screening's Role in Identifying Neonatal Complications.

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications.

Correlation between PAPP-A serum levels in the first trimester of pregnancy with the occurrence of gestational diabetes, a multicenter cohort study

ObjectiveThis study aimed to investigate the association between first-trimester Pregnancy-associated plasma protein A (PAPP-A) levels and subsequent gestational diabetes mellitus (GDM) development.MethodThe study was conducted on 5854 pregnant women who attended routine prenatal care. Maternal biomarkers, including PAPP-A and free beta hCG, were measured for all women in a referral laboratory and converted to MoM values. Pregnant women were divided into two groups, based on the serum concentration of PAPP-A, (PAPP-A > 0.4 (normal) and PAPP-A < 0.4 (low)). Data on the screening test for GDM and pregnancy outcomes were collected and analyzed with appropriate tests.ResultOf the 5854 pregnant women, 889 (15.19%) developed GDM. The maternal PAPP-A MoM concentrations were significantly lower in GDM cases compared to controls. Indeed, gestational age at delivery and birth weight were significantly lower (p < 0.001) in PAPP-A MoM < 0.4, and the rate of intrauterine growth restriction (IUGR) was significantly higher (p < 0.001). ROC analysis revealed that the sensitivity and specificity of MoM concentration for predicting GDM were 53.3% and 51.9%, respectively.ConclusionLower maternal PAPP-A in early pregnancy can lead to glucose intolerance and increase the risk of subsequent GDM development. In addition, decreased serum concentration of PAPP-A is significantly correlated to lower birth weight and IUGR.

Elevated first-trimester PAPP-A is a marker in high-risk pregnancies with an increased risk of placenta accreta in predicting adverse outcomes.

Our work aims to determine whether there is an association between first-trimester serum pregnancy-associated plasma protein A (PAPP-A) multiples of the median (MoM) value and placenta previa with or without placenta accreta spectrum disorders (PAS) in women. A retrospective analysis was performed on 267 patients who had first-trimester screening test results for aneuploidy, including nonadherent placenta previa (n=106), placenta previa with PAS (n=60), and control group (healthy pregnant women with previous cesarean section and normal placental location, n=101). To assess the significant difference between these groups, PAPP-A MoMs were compared. The median PAPP-A MoM of 1.96 in placenta previa with PAS was significant (>0.88) in nonadherent placenta previa and 0.89 in the control group (p<0.001). Serum PAPP-A was found to be significantly associated with the severity of bleeding, such that patients with severe bleeding of 1,500 mL or more (n=54) had a higher mean PAPP-A MoM (1.93±0.69; p<0.001). Furthermore, the mean PAPP-A MoM was found to be 1.96±0.74 in the hysterectomy group and 0.89±0.47 in the conservative management group, and the difference was found to be significantly higher (p<0.001). Elevated PAPP-A values in the first trimester of pregnancy may be a useful marker for identifying women at higher risk of PAS and adverse outcomes.

Correlation and predictive value of serum miR-146b-5p expression during the first trimester of pregnancy with pre-eclampsia

The aim of this study was to investigate the correlation and predictive value of serum miR-146b-5p expression during the first trimester of pregnancy with pre-eclampsia (PE). In total, 32 normal pregnant women (the control group) and 58 subjects with PE were randomly selected from eligible case data. The serum levels of miR-146b-5p, pregnancy associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) were then detected. Next, we established predictive models of single or multiple markers for PE. The levels of miR-146b-5p in the mild pre-eclampsia (mPE) and severe pre-eclampsia (sPE) groups were higher than the control group and there were significant differences between the three groups (F = 3.424, P = 0.037). The statistical results of the model before and after 200 times 10-fold cross-validation were as follows: miR-146b-5p (AUC = 0.723 vs AUC = 0.710); miR-146b-5p + BMI + MAP + free β-hCG MoM + PAPP-A MoM (AUC = 0.929 vs AUC = 0.851). We found that expression levels of miR-146b-5p in the first trimester were significantly higher in the serum of pregnant women with PE than in the normal pregnancy group. A prediction model in combination with miR-146b-5p and other markers improved the early predictive value for PE. IMPACT STATEMENT What is already known on this subject? Pre-eclampsia is a complex systemic disease with hypertension as the main clinical manifestation and causes extensive damage to the body. Some existing maternal biochemical markers have limited value in predicting PE, and new biomarkers with high sensitivity and specificity are urgently needed in clinical practice. There are a variety of abnormal expression miRNAs in PE, however, the relationship between miR-146b-5p and PE has yet to be fully elucidated. What do the results of this study add? We first found that expression levels of serum miR-146b-5p in the first trimester were significantly higher in PE than in a normal pregnancy group. A prediction model a combination of miR-146b-5p and other maternal characteristics and biochemical markers can improve the early predictive value for PE. What are the implications of these findings for clinical practice and/or further research? PE progresses rapidly and has become a severe target organ complication when discovered. Therefore, the early prediction of a high risk of PE, along with early intervention and prevention measures, are of great significance. Compared to maternal biochemical markers, combination of miR-146b-5p and maternal characteristics and biochemical markers can improve the early predictive value for PE.

Value of PAPP-A combined with BMI in predicting the prognosis of gestational diabetes mellitus: an observational study

The aim of this study was to investigate the potential of pregnancy-associated plasma protein A (PAPP-A) and clinical data in predicting gestational diabetes mellitus (GDM). Clinical data of 318 pregnant women with GDM and 200 healthy pregnant women were retrospectively analysed. The age, BMI and caesarean section in GDM were significantly higher than in normal group. Serum and placental levels of PAPP-A were significantly lower in GDM than in normal group. Pearson’s correlation analysis showed that serum levels of PAPP-A were negatively correlated with BMI and blood glucose level. Binary logistic regression analysis displayed that PAPP-A were the potential factors influencing GDM. The area under the ROC curve (AUC) for PAPP-A combined with BMI in predicting GDM was 0.941, significantly higher than that of the single one. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. Impact statement What is already known on this subject? GDM not only increases the risk of perinatal morbidity, but also results in an increased risk of long-term sequelae for both mother and child including diabetes, cardiovascular disease obesity. Previous data indicate that besides glycemic control in the second trimester, interventions initiated early in pregnancy can reduce the rate of GDM in pregnant women. The expression of PAPP-A in serum of GDM pregnant women was decreased in the first trimester. Whereas, whether PAPP-A can be as an early predictor of GDM is not clear. What do the results of this study add? The present study shows that PAPP-A MoM was less than 0.6757 in the first trimester of pregnancy is more prone to GDM. The potential of PAPP-A in the first trimester is limited in predicting GDM. PAPP-A combined with BMI is highly conductive for predicting GDM. What are the implications of these findings for clinical practice and/or further research? Early GDM prediction is crucial for prevention and management of GDM, to cope with the rising prevalence of GDM and reduce later life chronic disease of both mother and child. Based on the level of PAPP-A MoM and BMI, interventions such as lifestyle changes initiated early in pregnancy shouldbeenabledin pregnant women.

The predictive value of the first trimester combined test for gestational diabetes mellitus.

To investigate the predictive importance of first trimester combined test markers pregnancy-associated plasma protein-A (PAPP-A), human chorionic gonadotropin β (β-hCG) and nuchal translucency (NT) for gestational diabetes mellitus (GDM). Pregnant women which both first trimester combined test and GDM screening were performed during antenatal follow-up were included in this retrospective case-control study. The cases were divided into two groups as GDM screening positive and negative. Demographic, clinical and laboratory data of both groups were compared. Predictive tests were applied to the first trimester combined test data for the detection of GDM. A total of 378 patients, 171 (45.2%) in the control group and 207 (54.8%) in the GDM group. The age (control: 30.9 ± 5.2; GDM: 30.5 ± 5.1; p = 0.844) and NT (control: 1.254 ± 0.289; GDM: 1.319 ± 0.299; p = 0.074) data of the groups were statistically similar. MoM PAPP-A (GDM:0.967 ± 0.685; ontrol:1.191 ± 0.624; p < 0.001) and MoM f-βhCG (GDM: 0.9 ± 0.602; control: 1.103 ± 0.746; p = 0.001) levels of the GDM group were lower than the control group. In the binary logistic regression model, MoM PAPP-A and MoM f-βhCG variables were found to be effective on GDM. In the ROC analysis of these variables, the MoM PAPP-A (0.654) had the highest area under the curve. According to the optimum cut-off point (≤ 0.885) of the MoM PAPP-A, we found a sensitivity of 66.7% and a specificity of 65.50% for predicting GDM. Our study showed that serum PAPP-A and f-βhCG MoM values, which are among the first trimester combined test parameters, can be used in the early pregnancy period for the prediction of GDM.

An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population.

Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.2756A>G, MTRR: c.66A>G, RFC1: c.80C>T and TCN2: c.776G>C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin β (free-β-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and β-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C>T MTHFR and c.776G>C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G>C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and β-hCG MoM values remain independent risk factors for fetal-T21.

Low first trimester maternal serum PAPP-A concentrations in women with non-cavity-distorting intramural uterine fibroids.

Reliable aneuploidy risk estimation in first trimester is prominently interconnected with accurate assessment of maternal serum biomarkers. Some maternal factors like insulin-dependent diabetes, weight, and rhesus status are known to alter levels of these biomarkers. Adjustment of biomarker values for specific factor is crucial to avoid excessive invasive procedures or missed diagnoses. We aimed to investigate the effects of noncavity distorting intramural uterine fibroids on first trimester aneuploidy screening test maternal serum biomarkers. Pregnant women who underwent first trimester aneuploidy screening test in a single tertiary center between 2011 and 2020 were retrospectively assessed. One hundred ninety-eight women were found to have at least one noncavity distorting intramural uterine leiomyoma (Figo type 3-6) of at least 2cm diameter and remaining women were assigned as controls. First trimester aneuploidy screening test parameters were compared. Pregnancy associated plasma protein-A (PAPP-A) MoMs were found significantly lower in leiomyoma group in comparison to control group (1.19 ± 0.60 MoM vs. 1.40 ± 0.73 MoM, p=0.002). PAPP-A MoMs in women with leiomyomas larger than 5.5cm were significantly lower in comparison to both control group and women with ≤5.5cm leiomyomas (0.82 ± 0.376 vs. 1.40 ± 0.73, p < 0.001; 0.82 ± 0.376 vs. 1.33 ± 0.61 p < 0.001, respectively). PAPP-A MoM and size of leiomyoma were found inversely correlated when fibroid size exceeds 5.5cm (r=-0.467, p < 0.001). Noncavity distorting intramural uterine leiomyomas >5.5cm are associated with low first trimester PAPP-A MoMs (<0.5). PAPP-A concentrations are inversely correlated with fibroid size in women with >5.5cm intramural uterine leiomyomas. Fibroids ≤5.5cm are not associated with alterations in first trimester aneuploidy screening test parameters.

Prediction of Preeclampsia Using First-Trimester Uterine Artery Doppler and Pregnancy-Associated Plasma Protein-A (PAPP-A): A Prospective Study in Chhattisgarh, India

IntroductionPreeclampsia is a major contributor of maternal and perinatal morbidity and mortality. Uterine artery waveform and biomarkers like pregnancy-associated plasma protein-A (PAPP-A) may reflect the pathophysiology of preeclampsia. Thus, we aim to find out whether abnormal uterine artery pulsatility index (PI) and low serum PAPP-A in the first trimester can predict preeclampsia.MethodologyAntenatal women at 11-13+6 weeks of gestation visiting All India Institute Of Medical Science (AIIMS) in Raipur were enrolled after informed consent. Uterine artery Doppler was done with the early anomaly scan at 11-13+6 weeks. Serum levels of PAPP-A were analyzed. The women were followed up at intervals up to delivery. Incidence of preeclampsia and gestational hypertension was noted.ResultsThe incidence of preeclampsia was 12.7%, and that of gestational hypertension was 4.9%. The mean uterine artery PI among those who developed hypertension in pregnancy was 2.007, which was significantly higher than the unaffected group (p=0.01). The first-trimester uterine artery PI as a screening tool showed a sensitivity of 68%, specificity of 52.99%, and detection rate (DR) of 55.63%.The mean PAPP-A MoM of the affected group was 0.67 which was significantly higher than the unaffected group (p<0.001). The first trimester PAPP-A as a screening tool showed a sensitivity of 28%, specificity of 90.6%, and DR of 79.58%.ConclusionBoth the tests were concluded to be good predictors of hypertension in pregnancy. Identification of high-risk factors, screening, and surveillance are of utmost importance in order to predict preeclampsia and initiation of preventive therapy.

The relationship between first and second trimester biochemical parameters used to screen down syndrome and intrahepatic cholestasis of pregnancy

Objective: To assess the role of first and second-trimester screening biomarkers pregnancy-associated plasma protein-A(PAPP-A), free beta-human chorionic gonadotropin(free ß-hCG), estriol, alpha-fetoprotein and total β-hCG in the early diagnosis of intrahepatic cholestasis of pregnancy (ICP). Materials and Methods: Patients with ICP admitted to Mersin University Hospital for delivery between 2015 and 2019 and had first and second-trimester aneuploidy screening tests performed in the same facility were retrospectively assessed. Randomly 60 pregnant women without comorbid conditions during the same period were included as controls. Data regarding demographic characteristics, laboratory values including free ß-hCG and PAPP-A in first-trimester screening and total ß-hCG, estriol and alpha- fetoprotein in second-trimester screening were compared. Results: There were 46 eligible patients with ICP. In first trimester screening, it was found that PAPP-A MoM was significantly lower (0.89±0.55 vs. 1.94±0.73; p=0.035) while free ß-hCG MoM was significantly higher in ICP group when compared to controls (1.84±0.59 vs. 0.99±0.47; p=0.018). In second trimester screening, no significant difference was detected in aneuploidy markers between groups. For prediction of ICP development, first trimester free β-hCG &gt;1.44 MoM was found to have a sensitivity of 50%, a specificity of 80% and positive and negative predictive values of 33% and 88.9% respectively. Similarly first trimester PAPP-A values &lt;1.075 MoM was found to have 80% and 75% sensitivity and specificity with positive and negative predictive values of 75% and 44% respectively. Conclusion: Low PAPP-A MoM value and elevated free ß-hCG in first trimester seem to be associated with ICP development.

Performance of Fetal Medicine Foundation algorithm for first trimester preeclampsia screening in an indigenous south Asian population

BackgroundTo evaluate the performance of the Fetal Medicine Foundation (FMF) preterm preeclampsia (PE) screening algorithm in an indigenous South Asian population.MethodsThis was a prospective observational cohort study conducted in a tertiary maternal fetal unit in Delhi, India over 2 years. The study population comprised of 1863 women carrying a singleton pregnancy and of South Asian ethnicity who were screened for preterm pre-eclampsia (PE) between 11 and 14 weeks of gestation using Mean Arterial Pressure (MAP), transvaginal Mean Uterine Artery Pulsatility Index (UtAPI) and biochemical markers - Pregnancy Associated Plasma Protein-A (PAPP-A) and Placental Growth Factor.. Absolutemeasurements of noted biomarkers were converted to multiples of the expected gestational median (MoMS) which were then used to estimate risk for preterm PE < 37 weeks using Astraia software. Women with preterm PE risk of ≥1:100 was classified as as high risk. Detection rates (DR) at 10% false positive rate were calculated after adjusting for prophylactic aspirin use (either 75 or 150 mg).ResultsThe incidence of PE and preterm PE were 3.17% (59/1863) and 1.34% (25/1863) respectively. PAPP-A and PlGF MoM distribution medians were 0.86 and 0.87 MoM and significantly deviated from 1 MoM. 431 (23.1%) women had a risk of ≥1:100, 75 (17.8%) of who received aspirin. Unadjusted DR using ≥1:100 threshold was 76%.Estimated DRs for a fixed 10% FPR ranged from 52.5 to 80% depending on biomarker combination after recentering MoMs and adjusting for aspirin use.ConclusionThe FMF algorithm whilst performing satisfactorily could still be further improved to ensure that biophysical and biochemical markers are correctly adjusted for indigenous South Asian women.

Can first trimester pregnancy-associated plasma protein-A predict the surfactant needs of preterm neonates?

Low values of pregnancy associated plasma protein A (PAPP-A), have been shown to be associated with some poor gestational outcomes, especially those related to placental deficiency such as pre-eclampsia and fetal growth restriction as well as preterm labor. The aim of this study was to compare first trimester PAPP-A MoM values with the surfactant needs of newborns of pregnant women who had a preterm delivery. This study included 216 pregnant women who had a preterm delivery, who were found to be in the low-risk group based on their aneuploidy screening. The women were separated into two groups based on the surfactant receipts of their newborns. A record was made of the obstetric history, birth characteristics of the preterm infants, and whether or not there was a need for surfactant. A comparison of the PAPP-A values of the two groups revealed that the group that received surfactant had statistically significantly lower PAPP-A values (t(-3.97) = 0.203, p < 0.001). When the cut-off value of PAPP-A was taken as 1 MoM and the gestational age was analyzed together with the birth weight, PAPP-A alone was found to be a significant independent variable for the prediction of respiratory distress syndrome (RDS) (p = 0.031; OR:8.2 (1.2-55.6)). The result of this study demonstrated that PAPP-A MoM values may be significant in predicting the need for surfactant in RDS, which is a frequently seen condition in the neonatal period.

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 Combined Screening for Trisomies 21, 18, and 13 by Three Closed Chemiluminescence Immunoassay Analyzers (an Experiment on Iranian Pregnant Women)

Background: Pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (free β-hCG) as valuable biochemical biomarkers are used to screen down syndrome, Edwards syndrome, and Patau syndrome in the first trimester of pregnancy. Closed immunoassay analyzers are regarded as sophisticated platforms to measure biochemical biomarkers. This study compared the performance of three chemiluminescence analyzers when used for combined screening.Methods: The present cross-sectional study was conducted on 371 pregnant women within the age range of 20-47 years during 11+0 to 13+6 weeks of pregnancy referring to Dena laboratory in Tehran, Iran, during July 2018 and August 2018 using random selection. The biochemical biomarkers of PAPP-A and free β-hCG were assayed on Cobas, Immulite, and Maglumi analyzers. Benetech software as a commercial screening software was used to calculate the risks of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13). Deming regression, nonparametric spearman analysis, analysis of variance, and Chi-square test were performed to analyze the data.Results: For the screening population, although the three systems well correlated to PAPP-A and free β-hCG, the values of Maglumi were slightly higher than those reported for Cobas and Immulite. The multiples of the median (MoM) of PAPP-A and free β-hCG had a significant correlation on three platforms. There were no significant differences between the calculated risks of T21, T18, and T13 on the three systems. The sensitivity for all systems was reported as 50%. In addition, specificity and negative predictive value (NPV) were higher than 99% and 95%, respectively. Positive predictive value (PPV) was reported as less than 50%.Conclusion: The obtained results of the present study demonstrated that there were significant correlations between three different systems in terms of PAPP-A and free β-hCG values and MoMs. The sensitivity of all systems for all trisomies was 50%; however, the specificity of all systems was almost the same. The best PPV and NPV for T21 were on Cobas, Immulite, and Maglumi, respectively. The PPV and NPV of all systems for T18/13 were almost the same.

First trimester prenatal screening in multiple pregnancies. Part I: comparative analysis of serum proteins PAPP-A and p-hCG in pregnancies conceived spontaneously or by in vitro fertilization

Introduction. Serum proteins PAPP-A (pregnancy-associated plasma protein-A) and β-hCG (the в-subunit of human chorionic gonadotropin) levels are components of the 1st trimester combined screening aimed to detect fetal aneuploidies. In contrast to singleton pregnancies, where the values are well established, this is not the case in twins. Aim : a comparative analysis of serum proteins PAPP-A and β-hCG levels, as well as parameters PAPP-A MoM and β-hCG MoM in the first trimester during pregnancy with dichorionic diamniotic twins that occurred spontaneously or as a result of in vitro fertilization (IVF). Materials and methods . The study group included multiple pregnancies as a result of IVF procedure (n = 100) and spontaneous multiple pregnancies (n = 121) considered as controls. The levels of PAPP-A, β-hCG, PAPP-A MoM and β-hCG MoM were compared using nonparametric Mann-Whitney U test. Results. The PAPP-A MoM level resulted higher in the group of IVF twins (p = 0,007) compared to spontaneous twins: 1.28 [0.97; 1.89] vs. 1.12 [0.87; 1.40] (median [interquartile range]). There were no statistically significant differences in в-hCG levels between the groups of IVF twins and spontaneous twins. Conclusion. The results justify the need for further study of PAPP-A and β-hCG to establish their association with adverse outcomes in both groups of multiple pregnancies.

Are the first-trimester levels of PAPP-A and fb-hCG predictors for obstetrical complications in diabetic pregnancy?

Objective To assess the levels of pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (fb-hCG) in cases of diabetic pregnancy, to determine whether these biomarkers can be considered significant predictors for macrosomia, preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth in mothers with different types of pregestational diabetes mellitus (DM). Methods It was a retrospective cohort study. Study groups were presented: type 1 DM (n = 100), type 2 DM (n = 50), and controls (n = 25). At 11 + 0 to 13 + 6 week’s gestation, we recorded maternal characteristics and medical history, and performed a combined test for the detection of risk of chromosomal abnormalities. To assess the performance of the markers in the prediction of the main obstetrical complications (PE, IUGR, preterm birth, and macrosomia), receiver-operating characteristic (ROC) curves were produced and area under the curves was calculated. Results The study has shown that DM is associated with a high rate of perinatal complications: PE, IUGR, macrosomia, and preterm birth. The median level of PAPP-A was significantly lower in case of type 1 DM- 0.89 (inter quartile range (IQR), 0.51–1.1), and type 2 DM-0.88 (IQR, 0.42–1.15) compared to the unaffected group 1.03 (IQR, 0.96–1.12; p = .025). There were no significant differences in the fb-hCG multiples of the normal median (MoM; p = .14) between the diabetic and unaffected groups. More significant results were obtained when calculated by percentile: in diabetic pregnancies, PAPP-A and fb-hCG MoMs values were lower in the 5–10% ranges and higher in the 95% range, compared to the control group. ROC-analysis did not show any significant data that first-trimester PAPP-A and fb-hCG serum levels are predictors for PE, IUGR, macrosomia, and preterm birth. Conclusion The routine first-trimester serum screening of fetal Down syndrome cannot be used as a tool of risk identification for PE, IUGR, macrosomia, and preterm birth in case of diabetic pregnancy.

First-trimester placental function in levothyroxine-using pregnant women: a case-control study

We aimed to compare the pregnancy-associated plasma protein-A (PAPP-A) and the uterine artery pulsatility index (UtA PI) levels of euthyroid pregnant women using levothyroxine vs. a control group of uncomplicated pregnancies and to evaluate the effects of different levothyroxine dosages on pregnancy outcomes. We retrospectively evaluated 206 levothyroxine-using pregnant women by looking at their basic placental function markers and obstetric outcomes. A sample of 449 women whose pregnancies concluded with uncomplicated term deliveries composed of our control group. To examine the relationship between the levothyroxine dosages and the frequency of pregnancy complications, levothyroxine users were divided into different groups according to the 75, 100, and 150 mcg cutoffs. The median PAPP-A MoM levels of levothyroxine users were significantly lower at 0.94 vs. 1.11 (p < .001) and the median mean UtA PI was significantly higher than the control group at 2.08 vs. 1.74 (p < .0001). The median birth weight was significantly lower for the levothyroxine users’ group at 3292 g vs. 3427 g (p < .0001). Using 75, 100, and 150 mcg dose cutoffs, PAPP-A MoM, mean UtA PI and obstetric complication frequencies were not significantly different among levothyroxine users. Significant changes in placental function markers have been observed in euthyroid levothyroxine-using pregnant women during the first trimester. However, the frequency of obstetric complications does not appear to be dose dependent.

The effect of oral micronized progesterone on first trimester screening test markers and neonatal outcome

Objective: It was aimed to investigate whether or not nuchal translucency(NT) thickness, maternal serum free beta-human chorionic gonadotropin(β-hCG) and pregnancy-associated plasma protein-A(PAPP-A) levels may affected by the use of oral micronized progesterone(OMP) in first trimester pregnancies. Also we aimed to evaluate pregnancy outcome in pregnant women using OMP. Method: This study was performed retrospectively including 1192 pregnant women, between January 2015 and August 2017. Body mass index(BMI), maternal and gestational age, levels of maternal serum PAPP-A and free β-hCG, NT measurement and the crown–rump length(CRL), fetal sex, fetal birth weight, Apgar score 5thminute<7 and admission to neonatal intensive care unit(NICU) were evaluated. Results: Maternal characteristics, ultrasound and biochemical parameters, fetal characteristics and neonatal outcome were evaluated. There was no statistically significant difference for maternal age, BMI, gestational age, PAPP-A, β-hCG, CRL, NT thickness, fetal sex, fetal birth weight, Apgar score 5th minute <7 and the number of admission to NICU during the first 28 days. Conclusions: Our results suggest that in clinical practice, 1) it seems that using OMP cannot affect on NT, CRL and birth weight. 2) OMP cannot adversely affect on production of PAPP-A and β-hCG in vivo. 3) NT, serum PAPP-A and β-hCG levels and MoM values, which are markers of the first trimester screening test, do not change by using OMP. Therefore using OMP cannot affect reliability of the first trimester screening test in pregnancy with threatened abortion. 4) OMP does not look like adversely affect on poor neonatal outcome.