Serum PAPP-A Research Articles

PREDICTIVE MARKERS FOR ADVERSE PREGNANCY OUTCOMES: INSIGHTS FROM A PROSPECTIVE COHORT STUDY ON MATERNAL FACTORS, BIOMARKERS, AND UTERINE ARTERY DOPPLER RESULTS

Objective: Effective prediction tools are necessary for better outcomes when it comes to pregnancy-related complications such as intrauterine growth restriction (IUGR), pregnancy-induced hypertension (PIH), and premature birth. In order to improve early risk diagnosis and treatment, this study investigates relationships between maternal variables, first-trimester biomarkers, and second-trimester uterine artery Doppler findings. Methods: Correlations between demographic characteristics, maternal dual test indicators (serum beta-HCG, serum PAPPA), and uterine artery Doppler tests were examined in a prospective cohort study including 500 pregnant women. Statistical studies evaluated correlations with IUGR, PIH, and premature birth. Results: Serum beta-HCG levels below the 5th percentile correlated significantly with preterm birth (RR 2.3131, p = 0.0288). Low serum PAPP-A levels (<5th percentile) associated with PIH (RR 2.1447, p = 0.0204) and IUGR (RR 2.0953, p = 0.0002). Uterine artery Doppler indices (>0.58 RI) demonstrated associations with PIH (RR 2.2448) and IUGR (RR 1.6293). Diastolic notching correlated with preterm birth, PIH, and IUGR. Conclusion: The potential of serum beta-HCG, PAPP-A, and uterine artery Doppler indices as useful predictors of unfavorable pregnancy outcomes is highlighted by this study, which also highlights their use in early risk detection.

The influence of trophectoderm biopsy for preimplantation genetic testing in the serum level of first trimester biomarkers: PAPP-a, βhCG and PIGF

Research questionDoes trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A) affect maternal serum first trimester pregnancy biomarkers (PAPP- A, free β-hCG, PlGF)? DesignRetrospective cohort study, including all singleton pregnancies (n=9794) following either spontaneous conceived (SC) (n=8005) in vitro fertilization and fresh embryo transfers (IVF) (n=478) or frozen embryo transfer of non PGT-A (FET)(n=963) or PGT-A tested embryos (FET+PGT-A) (n=348). In all women with a viable pregnancy at 8-13.6 weeks of pregnancy, we measured serum levels of free β-hCG and PAPP-A . PlGF was measured in 3784 patients. These biomarkers were converted to a multiple of the expected normal median (MoM) for a pregnancy of the same gestational day. We calculated the medians for the multiple of the median and compared them. ResultsFree β-hCG did not differ according to the mode of conception. PAPP-A concentrations were significantly lower in in vitro fertilization and fresh embryo transfers (-0,1 Log10 MoM raw PAPP-A) when comparing to FET+PGT-A (-0,04 Log 10 MoM raw PAPP-A) and SC (-0,0187 Log 10 MoM raw PAPP-A) (p<0,05). PlGF levels were significantly lower in the FET+PGTA group (p<0.05). The difference in means adjusted by CRL was 4.6 pg/ml 95%CI [2.7-6.6] for SC, 3.5 pg/ml 95%CI [0.34-6.6] for IVF and 2.2 pg/ml 95%CI [0.06-4.4] for FET. ConclusionThis study demonstrates that trophectoderm biopsy for PGT-A has a significant impact on first trimester maternal serum PAPP-A and PIGF. This needs to be further validated since it may mislead the estimation of the first trimester risk of aneuploidies and preeclampsia.

Prediction of Gestational Diabetes Mellitus Risk in Early Pregnancy Using Antenatal Screening Biomarkers

Aim: In this study, we aimed to compare their success in predicting the risk of Gestational Diabetes Mellitus (GDM) using demographic (age, gravidity, parity), body mass index (BMI), first-trimester fasting blood glucose (FBG), thyroid-stimulating hormone (TSH), and antenatal screening biomarkers (dual and quadruple tests). Materials and Methods: In this study, 800 pregnant women who underwent a one-step 75 g Oral Glucose Tolerance Test (OGTT) and antenatal screening tests at a tertiary hospital between January 2017 and June 2020 were retrospectively investigated. After patients were divided into two groups based on their GDM screening test results, the examined parameters were compared between the GDM-Positive and GDM-Negative groups. Once the parameters significantly associated with GDM were determined, their clinical utility in the early diagnosis of GDM was investigated. Results: GDM was diagnosed in 159 (19.8%) of 800 patients. The GDM-Positive group had a higher age, gravidity, parity, BMI, and first-trimester serum FBG levels, as well as lower serum PAPP-A MoM levels than the GDM-Negative group (P

Serum hydroxysteroid (17beta) dehydrogenase 1 concentration in pregnant women correlates with pregnancy-associated plasma protein A but does not serve as an independent marker for preeclampsia†.

Hydroxysteroid (17beta) dehydrogenase 1 (HSD17B1) is a steroid synthetic enzyme expressed in ovarian granulosa cells and placental syncytiotrophoblasts. Here, HSD17B1 serum concentration was measured with a validated immunoassay during pregnancy at three time points (12-14, 18-20 and 26-28weeks of gestation). The concentration increased 2.5-fold (P < 0.0001) and 1.7-fold (P = 0.0019) during the follow-up period for control women and women who later developed preeclampsia (PE), respectively, and a significant difference was observed at weeks 26-28 (P = 0.0266). HSD17B1 concentration at all the three time points positively correlated with serum PAPPA measured at the first time point (first time point r = 0.38, P = 1.1 × 10-10; second time point r = 0.27, P = 5.9 × 10-6 and third timepoint r = 0.26, P = 2.3 × 10-5). No correlation was observed between HSD17B1 and placental growth factor (PLGF). Serum HSD17B1 negatively correlated with the mother's weight and body mass index (BMI), mirroring the pattern observed for PAPPA. The univariable logistic regression identified a weak association between HSD17B1 at 26-28weeks and later development of PE (P = 0.04). The best multivariable model obtained using penalized logistic regression with stable iterative variable selection at 26-28weeks included HSD17B1, together with PLGF, PAPPA and mother's BMI. While the area under the receiver operating characteristic curve of the model was higher than that of the adjusted PLGF, the difference was not statistically significant. In summary, the serum concentration of HSD17B1 correlated with PAPPA, another protein expressed in syncytiotrophoblasts, and with mother's weight and BMI but could not be considered as an independent marker for PE.

Early Trimester Maternal Serum β-hCG and PAPP-A Levels as Predictor of Hypertensive disorders of Pregnancy.

Hypertensive disorder of pregnancy is a mysterious condition. Even after extensive research, it is associated with high maternal as well as perinatal mortality and morbidity. The origin of hypertension in pregnancy is thought to be lying in the placenta. β-hCG and PAPP-A are glycoproteins produced from placenta. Therefore, these values are reported to be altered in hypertensive disorders of pregnancy. To determine the predictive value of early trimester serum β-hCG and PAPP-A levels for the development of hypertensive disorders of pregnancy. This is a prospective cohort study conducted at IMS and SUM Hospital, Bhubaneswar. Maternal serum β-hCG and PAPP-A levels were measured in all the singleton pregnant women at 11 + 0-13 + 6weeks. All these women were followed up till delivery to find out the development of hypertension. The outcome was matched with their respective biochemical markers and analyzed. Mean value for maternal serum β-hCG of the study population was found to be 48.95ng/ml with a range of 2-210ng/ml. Hence, maternal serum β-hCG value during 11-13weeks of pregnancy shows no correlation with the development of HDP later in pregnancy. The mean value of maternal serum β-hCG for women who developed HDP and those who did not develop the pathology was 48.13 ng/ml and 49.78 ng/ml, respectively (p = 0.61). Mean value of serum PAPP-A for the normotensive group was found to be 5.12mIU/ml and 3.76mIU/ml for women who developed HDP (p < 0.01). Low maternal serum PAPP-A determined at 11 + 0-13 + 6weeks has a better predictive value for the development of hypertensive disorders in pregnancy than β-hCG.

Efficacy of Labetalol Combined with Magnesium Sulfate in the Treatment of Hypertension during Pregnancy and its Effects on Serum PAPPA and PLGF Levels

Efficacy of Labetalol Combined with Magnesium Sulfate in the Treatment of Hypertension during Pregnancy and its Effects on Serum PAPPA and PLGF Levels

The effect of maternal asthma on serum PAPP-A levels and first trimester aneuploidy screening test running

The effect of maternal asthma on serum PAPP-A levels and first trimester aneuploidy screening test running

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

BackgroundCongenital heart defect (CHD) is the most common congenital abnormality, and it has long been a clinical and public health concern. Our previous findings have found Periostin (POSTN) and Pappalysin-1 (PAPPA) as potential biomarkers for fetal CHD. We aim to further elucidate POSTN's role in fetal heart development and explore the clinical applicability of POSTN and PAPPA as diagnostic marker for fetal CHD. This study is poised to establish a theoretical framework for mitigating the incidence of CHD and advance a novel approach for prenatal screening of fetal CHD.MethodsWe verified differential expression of POSTN and PAPPA in gravida serum and fetal amniotic fluid based on our previous research. We established the Postn knockout mouse by CRISPR/Cas9 to investigate whether Postn deletion leads to cardiac abnormalities in mice. Besides, we explored the mechanism of POSTN on heart development through Postn knockout mouse model and cell experiments. Finally, we established the logistic regression model and decision curve analysis to evaluate the clinical utility of POSTN and PAPPA in fetal CHD.ResultsWe observed a significant decrease in POSTN and increase in PAPPA in the CHD group. Atrial septal defects occurred in Postn−/− and Postn± C57BL/6 fetal heart, while ventricular septal defects with aortic saddle were observed in Postn± C57BL/6 fetal heart. Disruption of the extracellular matrix (ECM) in cardiomyocytes and multiple abnormalities in cellular sub-organelles were observed in Postn knockout mice. POSTN may positively regulate cell behaviors and unsettle ECM via the TGFβ-Smad2/3 signaling pathway. The combination of serum biomarkers POSTN and PAPPA with Echocardiogram can enhance the diagnostic accuracy of CHD. Furthermore, the comprehensive model including POSTN, PAPPA, and two clinical indicators (NT and age) exhibits significantly higher predictive ability than the diagnosis group without the use of serum biomarkers or clinical indicators.ConclusionsIt is the first evidence that Postn deletion leads to cardiac developmental abnormalities in fetal mice. This may involve the regulation of the TGFβ signaling pathway. Importantly, POSTN and PAPPA possess clinical utility as noninvasive prenatal promising screening indicators of CHD.

SARS-CoV-2 in early pregnancy-does it affect the aneuploidy screening markers and cause pregnancy loss?

It is known that vertical transmission of various infections poses a potential risk to the fetus, especially in early pregnancy. Potential effects of SARS-CoV-2 infection on early pregnancy and placental formation and functions still remain unknown. To determine the alterations of prenatal aneuploidy screening markers in a group of pregnant women who were SARS-CoV-2 positive during the first trimester. The secondary goal was to assess pregnancy loss rates. The study group consisted of pregnant women who were diagnosed with mild forms of SARS-CoV-2 infection before the screening test at any time in early pregnancy. The control group included pregnant women who were not diagnosed with SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 infection was detected by RT-PCR in the nasopharyngeal swab samples. Multivariate linear regression analysis was performed due to evaluate effect of SARS-CoV-2 infection on NT and serum aneuploidy screening parameters taking maternal age and gestational age which the COVID-19 RT-PCR test result was positive into account. We did not find any significant difference between the COVID-19-positive and COVID-negative groups in gestational age at screening, sonographic measurements of CRL, NT, and serum levels of PAPP-A, free hCG, and triple test serum markers even after accounting for maternal age and gestational age which the COVID-19 RT-PCR test result was positive. There was no statistically significant difference in pregnancy loss. We did not find any evidence for unfavorable prenatal biochemical, ultrasound markers of fetal aneuploidy screening tests, and pregnancy loss rates in our study group.

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening

IntroductionExtreme levels of either PAPP-A or free β-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. MethodsA total number of 8591 patients with singleton pregnancies between 11 + 0–13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free β-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. ResultsValues of PAPP-A ≥ 2,0 MoM and free β-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free β-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free β-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free β-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free β-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DiscussionPregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free β-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free β-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

The relationship between the first trimester maternal serum PAPP-A and β-hCG values and newborn intensive care needs in low-risk pregnancies.

The purpose of the study was to look at the connection between newborn intensive care requirements in low-risk pregnancies and maternal blood pregnancy-associated plasma protein (PAPP-A) and free human chorionic gonadotropin (hCG) levels, which are elements of screening tests within the first trimester. In the delivery unit of our hospital, pregnant women between the years of 18 and 35 had singleton pregnancies who delivered between 37 and 41 weeks of pregnancy between July 2021 and January 2022 were split into 2 groups. One hundred eighty two pregnant women with infants who required neonatal intensive care (NICU) were enrolled in the first group, whereas 890 pregnant women with infants who did not require NICU were enrolled in the second. These two groups' maternal blood PAPP-A and free hCG levels, which are among the first trimester screening procedures, were examined. Additionally, subgroup analysis were performed in terms of cesarean section indications and NICU admission indications. Logistic regression analysis and ROC analysis were performed with related variables for estimating NICU need. The mean serum PAPP-A value was found to be 0.91±0.34 multiples of the median (MoM) in the blood taken from the infant mothers who needed NICU, while the mean serum PAPP-A value in the blood taken from infant mothers who did not need NICU was 1.12±0.59 MoM (p<0.000). The PAPP-A MoM mean of the group with Apgar 5th minute score ≥8 (1.09±0.57) was higher than the PAPP-A mean (0.84±0.27) of the Apgar 5th minute score <7 group (p=0.013). According to the results of our study, in groups with a PAPP-A value below 0.95, the possibility of increased NICU need of newborns is higher. The low serum PAPP-A level, which is used as a screening test among pregnant women, demonstrates that it is successful in predicting perinatal outcomes in the low-risk pregnancy group.

Study on the Effect of B-Ultrasound NT Scan in Early Pregnancy Combined with Serum Screening in Early and Middle Pregnancy for Down Syndrome.

Objective Down syndrome (DS), also known as trisomy 21 syndrome, is a common and most harmful congenital chromosomal genetic disease. This study is aimed at exploring the effect of B-ultrasound NT scan in early pregnancy combined with serum screening in early and middle pregnancy for Down syndrome. Methods A total of 168 pregnant women who were diagnosed and treated in the obstetric clinic of our hospital from January 2019 to December 2021 were selected as the research objects. B-ultrasound NT scanning and serum detection in the early and middle trimester of pregnancy were performed, respectively. The accuracy of single detection and combined detection was analyzed and compared with the results of amniotic fluid cell chromosome examination as the gold standard. Results There were 4 cases of DS and 165 cases of non-DS. The serum PAPP-A, AFP, and UE levels in DS group were lower than those in non-DS group. β-HCG level and NT value were higher than those in non-DS group (all p < 0.05). Among 168 pregnant women, 5 cases were diagnosed as abnormal by ultrasonography, and 1 case was diagnosed as normal. By serological test, 20 cases with high risk of DS were diagnosed in 4 cases, and 148 cases with low risk of DS were diagnosed in 2 cases. Among 168 cases examined by serology combined with ultrasound, 10 cases with high risk of DS were found, and 4 cases were diagnosed; 158 cases had low risk of DS, and 0 cases were diagnosed. The negative predictive value, specificity, and coincidence rate of DS screening by the three methods were higher, and the positive predictive value and coincidence rate of combined screening were the highest (p < 0.05). The screening risk of Down syndrome was correlated with pregnancy outcome. The abnormal pregnancy rate in high-risk group was significantly higher than that in low-risk group, and the difference was statistically significant (p < 0.05). ROC curve showed that the sensitivity, specificity, and AUC of the combined detection were greater than those of serology and NT. Conclusion The application of B-ultrasound NT scan in early pregnancy combined with early and mid-term serum comprehensive screening in the screening of Down's infants is helpful to improve the diagnostic coincidence rate and reduce the occurrence of misdiagnosis.

Prediction of Prevalence Preeclamptic Women by the Screening of First-Trimester Biochemical Indices (PAPP-A andamp; Free B-HCG) and Third-Trimester Uterine Artery Doppler using ARC GIS in Khuzestan Province/Iran

Background & Objective: The objective of this study was to determine the association between the maternal serum concentration of PAPP-A and free B-HCG at 11-13(+6) weeks and the uterine artery pulsatility index (PI) at 30-34 weeks with the prediction of preeclampsia.Materials & Methods: This cohort study was performed on 882 women with singleton pregnancies from March 2018 to November 2020 at the university hospital (referred center) in Ahvaz/Khuzestan. Maternal serum PAPP-A and free B-HCG at 11-13(+6) weeks and uterine artery PI at 30-34 weeks were measured and compared between women with and without PE. MOM PAPP-A<0.4, MOM-free B-HCG>3, and uterine artery pulsatility index >1 (>95%) were considered abnormal. Then The effect of each of the indicators on preeclampsia was determined by overlaying the layers and performing logical calculations in ARC GIS software. The distribution of PE in different cities of Khuzestan province was investigated.Results: The mean MOM PAPP-A was significantly lower (1.05 vs. 1.21 P < /i>=0.03), and uterine artery PI was significantly upper (0.93 vs. 0.88 P < /i><0.01) in preeclamptic women compared to women without PE. No significant differences were observed in the mean MOM-free B-HCG between women with and without PE (1.33 vs. 1.2 P < /i>=0.667). The highest percentage of PE was in two regions of Ahvaz (80%), but concerning women referred from different cities was in Andimeshk (75%). Conclusion: A low level of maternal serum PAPP-A and increased uterine artery PI promoted the chance of developing PE. The highest prevalence of PE was in two regions of the center of Khuzestan province, and the most preferred due to PE in different cities was in Andimeshk.

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-β1 in maternal serum samples using ELISA technique. Serum protein markers TGF-β1, sENG and PAPP-A were significantly increased (p < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-β1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted. Impact statement What is already known on this subject? Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders. What do the results of this study add? The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension. What are the implications of these findings for clinical practice and/or further research? Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities.

Serum PAPP-A and Maternal Risk Factors in Prediction of SGA: A Retrospective Study

Serum PAPP-A and Maternal Risk Factors in Prediction of SGA: A Retrospective Study

Alterations in the fecal microbiota and serum metabolome in unstable angina pectoris patients.

Unstable angina pectoris (UAP) is a type of Coronary artery disease (CAD) characterized by a series of angina symptoms. Insulin-like growth factor 1 (IGF-1) system may be related to CAD. However, the correlation between the IGF-1 system, metabolism, and gut microbiota has not been studied. In the present study, we investigated the alterations of serum IGF-1 system, metabolomics, and gut microbiota in patients with UAP. Serum and stool samples from healthy volunteers and UAP patients were collected. Serum metabolomics, PAPP-A, IGF-1, IGFBP-4, STC2, hs-CRP, TNF-α, and IL-6 were detected in serum samples by LC-MS, and commercial ELISA kits, respectively. Fecal short-chain fatty acids (SCFAs) were measured by gas chromatography. 16S rDNA was used to measure the changes of the gut microbiota. The correlation of the above indicators was analyzed. There were 24 upregulated and 31 downregulated metabolites in the serum of UAP patients compared to those in the controls. Pathway analysis showed that these metabolites were enriched in pathways including linoleic acid metabolism, amino acid metabolism, starch metabolism, sucrose metabolism, and citrate cycle (TCA cycle), etc. Additionally, the UAP patients had lower fecal levels of 2-hydroxyisobutyric acid and succinic acid. 16S rDNA sequencing results showed that the relative abundances of Bacteroidetes, Synergistetes, Lactobacillaceae, Burkholderiaceae, Synergistaceae, and Subdoligranulum were significantly higher in the UAP patients than the healthy subjects. Moreover, the UAP patients had lower serum IGF-1, IGFBP-4, and STC2 and higher serum inflammatory cytokines (hs-CRP, TNF-α, and IL-6) levels than the healthy controls. Furthermore, there was a strong correlation between serum amino acids and IL-6, which played an important role in the development of UAP. These results indicated that the UAP patients had decreased serum IGF-1 level and imbalanced amino acids metabolism, which may be caused by the altered gut microbiota. It may provide a new therapeutic strategy for unstable angina pectoris.

Associations between Nausea and Vomiting in Pregnancy, Disgust Sensitivity, And First-Trimester Maternal Serum Free-β hCG and PAPP-A

Associations between Nausea and Vomiting in Pregnancy, Disgust Sensitivity, And First-Trimester Maternal Serum Free-β hCG and PAPP-A

VP28.07: Impact of confined placental mosaicism on outcome of pregnancy

To assess the incidence of confined placental mosaicism (CPM) on CVS and amniocentesis in our population and to study the impact of CPM on the outcome of pregnancies with a structurally normal fetus at mid trimester anomaly scan and the association of abnormal first trimester serum biochemistry with CPM. This is a single centre study where all pregnancies that had an invasive procedure ie CVS or amniocentesis before 20 weeks of gestation from January 2011 till December 2020 were considered. The study included pregnancies that had mosaic pattern on CVS or amniocentesis. The incidence of CPM on CVS and amniocentesis was calculated. Fetal ultrasound in all trimesters, maternal serum biochemistry in the first trimester, presence of fetal growth restriction (FGR) and postnatal outcome were obtained. During the study period, of the 2081 Amniocentesis procedures 1 (0.05%) had CPM with tetraploidy mosaic confirmed by postnatal karyotype with normal outcome. Of 1144 CVS procedures performed 10/1144 (0.9%) were detected to have a mosaic pattern. 5/10 mosaic pattern obtained in pregnancies with fetal structural abnormalities were terminated before amniocentesis could be performed. 5/10 (0.44%) had structurally normal fetuses and hence Amniocentesis could be performed to confirm CPM. Of the four where first trimester serum biochemistry was available, three (75%) cases had low maternal serum PAPP-A (< 0.3). 2 of 5 cases had Trisomy 18, one had Trisomy 16 and one had Trisomy 21 mosaic pattern, all of which had normal antenatal and postnatal outcomes. 1/5 pregnancies had Trisomy 16 mosaic pattern which was found to have severe early onset FGR at 18 weeks and was terminated. Hence, 1/5 pregnancies with CPM had poor fetal outcome. The incidence of CPM in our study was about 0.44% on CVS and that on amniocentesis 0.05%. FGR was the only antenatal complication. We did not observe any maternal complications. Low maternal serum PAPP-A levels may indicate a higher possibility of obtaining a mosaic pattern on a CVS.

Metabolic improvement after gastric bypass correlates with changes in IGF-regulatory proteins stanniocalcin-2 and IGFBP-4

BackgroundPregnancy-associated plasma protein-A (PAPP-A) is an enzyme that increases IGF-activity through cleavage of IGF-binding proteins (IGFBPs), primarily IGFBP-4, whereby bound IGF-I becomes released as a free molecule. The enzymatic activity of PAPP-A is irreversibly suppressed by the glycoprotein stanniocalcin-2 (STC2). Pre-clinical and clinical studies suggest that the STC2 – PAPP-A – IGFBP-4 axis is important in controlling local IGF-action. STC2, PAPP-A and IGFBP-4 are expressed in adipose tissue, and as bariatric surgery markedly reduces the amount of fat, we found it relevant to study the impact of Roux-en-Y gastric bypass (RYGB) on circulating concentrations of this IGF-regulatory network. MethodsAnalysis of fasting blood samples from 20 obese subjects, hereof 10 with preoperative type 2 diabetes, investigated before RYGB, and 1 week, 3 months and 12 months post-surgery. Members of the IGF-system were analyzed by immunoassays, bioactive IGF by cell-based IGF-I receptor activation assay. We compared changes in IGF-system components with changes in fasting plasma insulin and glucose, and HbA1c. ResultsPAPP-A remained unchanged, but STC2 decreased following RYGB (p < 0.05). The PAPP-A substrate IGFBP-4 declined (p < 0.01), whereas levels of PAPP-A specific IGFBP-4 fragments increased (p < 0.05), indicating an increased PAPP-A enzymatic activity post-RYGB. Further, the reduction in intact IGFBP-4 correlated with increased levels of bioactive IGF (p < 0.05). In multivariable regression analyses, an improved glucose metabolism correlated with reductions in STC2 and IGFBP-4, and with increases in bioactive IGF and IGF-I (p < 0.05). ConclusionAfter 12 months, RYGB caused reduced serum concentrations of intact IGFBP-4 and STC2, whereas serum PAPP-A remained at pre-operative levels. However, concentrations of PAPP-A generated IGFBP-4 fragments increased, pointing to an overall increased PAPP-A enzymatic activity following RYGB. Notably, reductions in intact IGFBP-4 and STC2 associated with improvements in glucose metabolism. Therefore, we propose that STC2 and IGFBP-4 are involved in the metabolic improvement that follows RYGB.

Association between low first trimester maternal serum PAPP-A levels and presence of unilateral or bilateral uterine artery diastolic notches

Objective Uterine artery impedance is known to have an effect on first trimester aneuploidy screening biomarkers. In this study we aim to compare first trimester screening parameters in women with and without uterine artery diastolic notches. Methods This retrospective case control study was conducted in a single tertiary center by obtaining medical records of women that admitted for first trimester pregnancy follow-up. Singleton pregnancies without structural anomalies, chromosomal anomalies and obstetric complications were included in the study. 268 women with first trimester unilateral uterine artery diastolic notches are constituted study group 1, 149 women with bilateral uterine artery diastolic notches constituted study group 2. 200 women were randomly selected as control group. Results Significantly decreased PAPP-A levels were found in both study groups. PAPP-A levels were even lower in women with bilateral notches in comparison to unilateral notches. Fetal birth weights and gestational ages at birth were also found significantly lower in study groups. Beta human chorionic gonadotropin levels and nuchal translucency measurements were found similar. Prevalence of false positive first trimester aneuploidy screening test results were significantly higher in women with bilateral uterine artery diastolic notches. Conclusion Presence of first trimester uterine artery diastolic notches, particularly the presence of bilateral diastolic notches, is related with decreased PAPP-A levels in first trimester aneuploidy screening and lead to higher false positive rates in first trimester aneuploidy screening and consequently more unnecessary invasive procedures.