Low Serum Pregnancy-associated Plasma protein-A Research Articles

Can we improve the outcome of pregnancies with low serum PAPP-A in the first trimester?

Low birth weight is associated with various complications, and recent findings rely on the fact that micronized progesterone supplementation leads to improved birth weight, which is crucial for addressing concerns related to fetal growth. Objective This study aimed to assess the impact of micronized progesterone (VMP4) supplementation on pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) values during first-trimester screening. Methods Out of 8933 patients evaluated, 116 pregnant women with low PAPP-A concentrations in their blood and no fetal chromosomal anomalies (CAs) were included. Three groups were formed: group 1 received VMP4 from 11 to 16 weeks (29 women, 25%), group 2 received VMP4 from 11 to 36 weeks (25 women, 21.5%), and group 3 (62 women, 53.5%) served as controls without receiving progesterone. Results Results indicated that group 3 had higher rates of complications, including miscarriages (16.37%), preterm delivery (17.8%), and fetal developmental abnormalities (19.4%). Birthweight variations were elevated in pregnancies without progesterone, contrasting with lower variations in VMP4 groups. Group 2, receiving VMP4 until 36 weeks, reported the lowest incidence of abortion and preterm birth (PB), along with the highest mean birth weight. Conclusions The conclusion suggests that 200 mg per day of VMP4 up to 36 weeks of supplementation led to fewer placental-related complications in women with very low PAPP-A at first-trimester screening (0.399 MoM). By reporting lower rates of miscarriages, PBs, and fetal developmental abnormalities in the micronized progesterone-treated groups, the study suggests a potential reduction in complications.

Study on the Relationship and Predictive Value of First-Trimester Pregnancy-Associated Plasma Protein-A, Maternal Factors, and Biochemical Parameters in Gestational Diabetes Mellitus: A Large Case-Control Study in Southern China Mothers.

To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers. This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free β-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11-13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24-28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test. GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53-0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68-0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P<0.001). A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.

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.

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.

Low maternal serum pregnancy-associated plasma protein-A as a risk factor of preeclampsia.

Low levels of pregnancy-associated plasma protein-A (PAPP-A) might be associated with abnormal placentation, leading to the development of preeclampsia during late gestation. We aimed to determine the association between low serum PAPP-A levels and rates of preeclampsia in Thai women with otherwise low-risk pregnancies. A cohort study was conducted on consecutive singleton pregnancies undergoing first trimester screening for fetal Down syndrome at a tertiary centre hospital. A prospective database was assessed for patient records, including PAPP-A levels, pregnancy outcomes and obstetrics complications. Pregnancies with potential causes of preeclampsia were excluded. Enrolled women were categorised into two groups: women with normal PAPP-A levels (≥ 10th percentile; control group); and those with low PAPP-A levels (< 10th percentile; study group). The main outcome measure was rate of preeclampsia. Of 6,887 women screened, 3,830 were available for analysis and 167 were excluded due to potential confounders. Of the remaining 3,663 women enrolled, 357 women were categorised as having low PAPP-A levels and 3,306 had normal PAPP-A levels. The prevalence of preeclampsia (8.4% vs. 2.6%) and early-onset preeclampsia (i.e. before 34 weeks of gestation) (1.1% vs. 0.1%) was significantly higher (relative risk 3.27 and 9.26, respectively) in women from the study group than in the control group. Pregnancy with PAPP-A levels < 10th percentile was significantly associated with an increased risk of preeclampsia that tended toward early development. Therefore, pregnant women with low PAPP-A levels in the first trimester should be considered to be at increased risk of preeclampsia.

Adverse pregnancy outcome in patients with low pregnancy-associated plasma protein-A: The Indian Experience.

The aim of our study was to examine the association of low pregnancy-associated plasma protein-A (PAPP-A) with adverse pregnancy outcome. A total of 1640 consecutive pregnant women between 9(+5) and 13(+6) weeks of pregnancy were recruited. One hundred and thirty women with PAPP-A levels < 0.4 multiple of median were followed till delivery and the outcome information was obtained for fetal loss, birthweight, growth restriction, preterm birth, reduced liquor and development of pre-eclampsia. During the study period, 130 (7.92%) women had low PAPP-A and were considered as cases and 200 women with normal PAPP-A were controls. Intrauterine growth restriction was observed in 28 (21.54%) cases as compared to 10 (5%) controls. Pre-eclampsia presented in 24 (18.46%) cases and in 18 (9%) controls. Twenty (15.38%) cases had preterm delivery compared to 12 (6%) controls. Fifty-six (43.08%) cases delivered low-birthweight babies compared to 22 (11%) controls. Thus, the incidence of intrauterine growth restriction, preterm birth and low birthweight was significantly more in the cases as compared to the control group. PAPP-A is a valuable analyte for predicting risk of adverse pregnancy outcome and women with low serum PAPP-A levels would benefit from closer surveillance.

Obstetrical complications associated with first‐trimester screening markers in twin pregnancies

The aim of this retrospective study was to investigate the relation between perinatal complications in twin pregnancies and the combination of first-trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (β-hCG) levels. The study was conducted at the Perinatology Department of Baskent University between January 2005 and December 2011. In total, 104 patients with twin pregnancies were recruited. The association of first-trimester maternal serum-screening markers with perinatal complications was investigated for small-for-gestational-age (SGA) fetuses or intrauterine growth restriction (IUGR), preterm delivery (before 34 weeks of gestation), pregnancy-induced hypertension (PIH), and growth discordance between fetuses. Low serum PAPP-A (below 10th percentile) levels were not correlated with preterm labor, PIH, or IUGR in twin gestations. Elevated free β-hCG levels (>90th percentile) were linked to increased rates of PIH and small-for-gestational-age fetuses or IUGR. Elevated first-trimester free β-hCG was related to adverse pregnancy outcomes in twin pregnancies, whereas low PAPP-A levels were not linked to adverse pregnancy outcomes.

Low pregnancy associated plasma protein-A in the 1st trimester: Is it a predictor of poor perinatal outcome?

The objective of the study was to examine the predictive value of pregnancy associated plasma protein-A (PAPP-A) as a marker of poor pregnancy outcome. Databases at the University Hospital Lewisham, were used retrospectively to identify singleton pregnancies, which underwent 1st trimester combined screening between July 2008 and April 2010 and were found to have PAPP-A levels ≤ 0.4MoM. The perinatal courses of these pregnancies (n = 315) were evaluated for signs of adverse perinatal outcome and compared with a matched control group of pregnancies (n = 330) with normal PAPP-A levels. Results showed that women with low serum PAPP-A were at increased risk of adverse pregnancy outcome compared with the control group (OR 2.4, p = 000.1). They were also more likely to suffer fetal loss (OR 6.2, p = 0.001) in the form of miscarriage (OR 2.7, p = 0.110) and stillbirth (OR 2.4, p = 0.001). It was concluded that serum PAPP-A is a marker for poor pregnancy outcome and women with low serum PAPP-A levels would benefit from increased monitoring of their pregnancies.

Low pregnancy associated plasma protein-a (PAPP-A) in the first trimester – is it a predictor of poor perinatal outcome?

AimTo examine the predictive value of pregnancy associated plasma protein (PAPP-A) for various markers of poor pregnancy outcome.MethodDatabases at University Hospital Lewisham were used retrospectively to identify all singleton pregnancies...

Prediction of miscarriage and stillbirth at 11–13 weeks and the contribution of chorionic villus sampling

To derive models for estimating risk of miscarriage and stillbirth from maternal characteristics and findings of first-trimester screening for aneuploidies and to define the procedure-related risk of chorionic villus sampling (CVS) after adjusting for these factors. We examined 33 856 singleton pregnancies at 11(+0) to 13(+6) weeks, and in 2396 CVS was carried out. Logistic regression analysis was used to examine the factors contributing to miscarriage and stillbirth. There were 33 310 (98.4%) livebirths, 404 (1.2%) miscarriages and 142 (0.4%) stillbirths. Models combining maternal characteristics, nuchal translucency, pregnancy-associated plasma protein-A (PAPP-A) and flow in the ductus venosus detected 36.9% of miscarriages and 35.2% of stillbirths, at a 10% false-positive rate. The risk of miscarriage and stillbirth increased with maternal age and weight, in women of African racial origin, in those with previous miscarriages or stillbirths and in those with low serum PAPP-A and reversed A-wave in the ductus venosus. The risk of miscarriage increased in women with pre-existing diabetes mellitus, in those conceiving on ovulation-induction drugs and in those with high fetal nuchal translucency, and the risk of stillbirth increased in women with chronic hypertension and in cigarette smokers. The expected number of miscarriages and stillbirths in the CVS group and the models derived from the non-CVS group were 45 (95% prediction intervals 32-58) and 18 (95% prediction intervals 9-26), respectively. These expected numbers were not significantly different from the observed 44 and 15 cases (p = 0.881 and 0.480), respectively. A high proportion of fetal losses can be predicted at 11 to 13 weeks. A model for such predictions can be used to assess the procedure-related risks from CVS.

First‐trimester umbilical vein blood flow in pregnancies with low serum pregnancy‐associated plasma protein‐A levels: an early predictor of fetal growth restriction

To investigate umbilical vein blood flow (UVBF) during the first trimester in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate umbilical vein (UV) diameter, time-averaged maximum velocity (TAMXV) and UVBF values to the subsequent development of fetal intrauterine growth restriction (IUGR). UVBF assessment was performed at 11 + 0 to 13 + 6 weeks' gestation in 102 singleton pregnancies with PAPP-A concentrations of < 0.3 multiples of the median. UV diameter, UV-TAMXV and UVBF were calculated and analyzed in relation to pregnancy outcome. Pregnancy outcomes were: 51 pregnancies with birth weight ≥ 10(th) centile (Group A), 30 pregnancies with birth weight < 10(th) centile with normal Doppler in the umbilical artery throughout gestation (Group B) and 21 pregnancies with birth weight < 10(th) centile and abnormal umbilical artery Doppler later in gestation (Group C). No differences were found in PAPP-A levels between groups. Group C fetuses exhibited significantly lower values of UV-TAMXV (z-score - 1.99 SDs, t = 8.527, P ≤ 0.0001) and UVBF (z-score - 0.97 SDs, t = 7.420, P ≤ 0.0001) in comparison with normal reference ranges, while no differences were found in Groups A or B. Decreased UV-TAMXV and UVBF at 11 + 0 to 13 + 6 weeks' gestation identify fetuses at risk of developing IUGR among pregnancies with low levels of PAPP-A.

Histomorphometric characteristics of first trimester chorionic villi in pregnancies with low serum pregnancy-associated plasma protein-A levels: relationship with placental three-dimensional power doppler ultrasonographic vascularization

Objective. To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization.Methods. Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11 + 0 to 13 + 6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system.Results. Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p = 0.005) and a smaller capillary diameter (p = 0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r = 0.51, p = 0.03; FI: r = 0.48, p = 0.04; VFI: r = 0.56, p = 0.01).Conclusions. Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.

Correlation between First-Trimester Maternal Serum Markers, Second-Trimester Uterine Artery Doppler Indices and Pregnancy Outcome

Aims: The aim of this study was to assess the correlation between first trimester maternal serum free beta-human chorionic gonadotropin (fBHCG), pregnancy-associated plasma protein A (PAPPA), second-trimester uterine artery (UA) Doppler measurements and adverse pregnancy outcomes. Methods: Serum levels of PAPPA and fBHCG were determined at the first trimester, and patients underwent bilateral UA Doppler assessments at 20–25 weeks of gestation. A serum PAPPA level <0.4 MoM was termed as low and the abnormal Doppler findings were the presence of bilateral notches and RI >0.52 (mean) or unilateral notch and RI >0.66 (90th percentile). Results: Mean PAPPA level was significantly lower in cases with unilateral or bilateral notches (1.09; 0.79 and 0.80 MoM for 0, 1 and 2 notches, p < 0.001). Fifty-two cases (12.8%) had a low PAPPA level; in this group the incidence of abnormal Doppler was significantly higher (34.6 vs. 18.4%, p = 0.011). In the presence of abnormal Doppler in a case with a low serum PAPPA the risk of pregnancy-induced hypertension (OR = 4.56, p = 0.0067), low birth weight (OR = 6.8, p = 0.0002) and the risk of at least one complication (OR = 7.6, p = 0.00001) were significantly high. Conclusion: Combination of first- and second-trimester findings might improve the efficiency of screening for pregnancy complications.

Is there a relationship between cord blood pregnancy-associated plasma protein-A and birth weight and length?

Background Infants whose mothers had low serum pregnancy-associated plasma protein-A (PAPP-A) in the first trimester were observed to have intrauterine growth retardation. Aim Suggesting that PAPP-A plays an important role in the availability and activity of insulin-like growth factors (IGFs), which affect growth, we aimed to investigate cord blood PAPP-A levels of infants with different birth lengths and weights. Study design and outcome measures The study included 97 full-term, live-birth neonates. After birth, their lengths and weights were measured. Cord blood PAPP-A levels were measured with an ultra sensitive enzyme-linked immunosorbent assay (ELISA). Results There was a significant negative correlation between cord blood PAPP-A levels and birth weight ( r = − 0.23; P = 0.023) and length ( r = − 0.24; P = 0.016). Using the classification made according to their length, it was found that newborns with short lengths had significantly higher mean PAPP-A levels than neonates with normal and long lengths ( P = 0.022; P = 0.002, respectively), whereas the difference between infants with normal lengths and infants with long lengths was not found to be statistically significant ( P > 0.05). On the other hand, there was a difference between the mean PAPP-A levels of the neonate groups classified according to weight; however, these differences were not statistically significant ( P > 0.05). Conclusion We concluded that increased cord blood PAPP-A levels were associated with birth length and weight decreases; however, PAPP-A levels affected birth length more than birth weight.

Serum parameters and nuchal translucency in first trimester screening for fetal chromosomal abnormalities.

To assess the relation between serum parameters and nuchal translucency in pregnancies affected by fetal aneuploidy in the first trimester. Retrospective study of different serum parameters collected prior to chorionic villus sampling and measurement of nuchal translucency in relation to fetal aneuploidy. Switzerland (German and Italian sector) and Bregenz, Austria. One thousand one hundred and fifty-one women aged 25 to 44 years at 10 to 13 weeks of gestation undergoing chorionic villus sampling, mostly for advanced maternal age. Fetal aneuploidy was found in 23 pregnancies including four cases of trisomy 21, five of trisomy 18 and one case of trisomy 13. Fetal karyotype, serum levels of free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and alpha-fetoprotein and the measurement of nuchal translucency. Serum PAPP-A was decreased in all common chromosomal abnormalities. Free beta-hCG levels were increased in trisomy 21 but decreased in trisomy 18, whereas alpha-fetoprotein was low in trisomy 21, 18 and other chromosomal abnormalities. Nine of twenty-three abnormal embryos had evidence of an increased nuchal translucency. Nuchal translucency, however, did not seem to be associated with any alteration in the levels of the biochemical parameters in either chromosomally normal or abnormal embryos. A low serum PAPP-A or an increased nuchal translucency was seen in two-thirds of all pregnancies with chromosomal abnormalities. A nuchal translucency > or = 3 mm and depressed serum PAPP-A levels have a good predictive value in the detection of fetal aneuploidy at 10 to 13 weeks of pregnancy. Serum free beta-hCG and alpha-fetoprotein levels may give additional information. An increased nuchal translucency was not associated with altered serum parameters. This would allow these different markers to be used in combination.

Serum PAPP-A and free beta-hCG are first-trimester screening markers for Down syndrome.

Serum measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta-human chorionic gonadotrophin (hCG) subunit were made in 13 women with Down syndrome (DS) pregnancies and six other women with fetal aneuploidy ascertained at chorionic villus sampling (CVS), as well as 89 women with contemporaneous normal control pregnancies. Median serum PAPP-A measurements (0.31 MOM, 95 per cent confidence interval (CI) 0.22-0.65 vs. normal 1.06, 95 per cent CI 0.89-1.20) were lower and free beta-hCG subunit measurements (1.13 MOM, 95 per cent CI 0.93-2.63 vs. normal 0.91, 95 per cent CI 0.79-1.03) were higher at statistically significant levels. Receiver operator characteristics (ROC) curves showed that the highest sensitivity for detection, 71.2 per cent (95 per cent CI 54.7-87.6 per cent), was for depressed PAPP-A levels; the combination of low serum PAPP-A levels, maternal age, and elevated free beta-hCG levels yielded a detection rate of 78.9 per cent (95 per cent CI 64.9-92.8 per cent) of the affected pregnancies at 8-12 weeks' gestation.