Low Pregnancy-associated Plasma protein-A Levels Research Articles

Low PAPPA and Its Association with Adverse Pregnancy Outcomes in Twin Pregnancies: A Systematic Review of the Literature and Meta-Analysis

Background: It is well established in the literature that pregnancy-associated plasma protein-A (PAPP-A) is linked to several adverse pregnancy outcomes, including pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB) in singleton pregnancies. However, data regarding such an association in twin pregnancies are lacking. The primary goal of this systematic review and meta-analysis was to assess the potential value of low PAPP-A levels in the prediction of the subsequent development of hypertensive disorders of pregnancy (HDPs), PTB, and small for gestational age (SGA)/FGR fetuses in twin pregnancies and investigate its association with the development of gestational diabetes, intrauterine death (IUD) of at least one twin, and birth weight discordance (BWD) among the fetuses. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 July 2024. All observational studies reporting low PAPP-A levels after the performance of the first-trimester combined test as part of the screening for chromosomal abnormalities with reported adverse pregnancy outcomes were included. Results: The current systematic review encompassed a total of 11 studies (among which 6 were included in the current meta-analysis) that enrolled a total of 3741 patients. Low PAPP-A levels were not associated with HDPs (OR 1.25, 95% CI 0.78, 2.02, I-square test: 13%). Low PAPP-A levels were positively associated with both the development of preterm birth prior to 32 (OR 2.85, 95% CI 1.70, 4.77, I-square test: 0%) and 34 weeks of gestational age (OR 2.09, 95% CI 1.34, 3.28, I-square test: 0%). Furthermore, low PAPP-A levels were positively associated with SGA/FGR (OR 1.58, 95% CI 1.04, 2.41, I-square test: 0%). Prediction intervals indicated that the sample size that was used did not suffice to support these findings in future studies. Conclusions: Our study indicated that low PAPP-A levels are correlated with an increased incidence of adverse perinatal outcomes in twin pregnancies. Identifying women at elevated risk for such adversities in twin pregnancies may facilitate appropriate management and potential interventions, but additional studies are required to identify the underlying mechanism linking PAPP-A with those obstetrical complications.

PAPP-A Levels and IGF-1 Levels in Early-Onset Preeclampsia and Late-Onset Preeclampsia

Introduction: The pathophysiology of preeclampsy is not yet fully understood, but failure of tropoblastinvasion and placentation, which is influenced by factors such as pregnancy-associated plasma proteinA (PAPP-A) and insulin-like growth factor 1 (IGF-1), is thought to play a role.Aims: This study aimed to explore the difference in PAPP-A and IGF-1 levels between Early OnsetPreeclampsia (PEAD) and Late Onset Preeclampsia (PEAL) assuming that the role of PAPP-A andIGF-1 is more significant in the pathogenesis of PEAD than PEAL.Methods: This is an analytical observational study with a cross-partition comparative study design.Clinical data were obtained at Dr. M. Djamil Padang Hospital, while PAPP-A and IGF-1 levels weremeasured at the Biomedical Laboratory of the Faculty of Medicine, Andalas University. Samples aretested according to reagent procedures and analyzed by experts.Results: Average PAPP-A levels were 2.45+0.35 pg/mL in the early onset preeclampsy group and2.85+0.50 pg/mL in the late onset preeclampsy group. These two levels differed statisticallysignificantly (p=0.006). That means that low levels of PAPP-A are associated with and play a role inthe pathogenesis of early onset preeclampsy. Average IGF-1 levels were 4.66+0.91 pg/mL in the earlyonset preeclampsy group and 5.39+0.74 pg/mL in the late-onset preeclampsy group. These two levelsdiffered statistically significantly (p=0.010). That means that low levels of IGF-1 are associated withand play a role in the pathogenesis of early onset preeclampsy. PAPP-A levels were significantlypositively correlated with IGF-1 levels (p=0.000).Conclusion: PAPP-A levels are lower in PEAD than PEAL, as are IGF-1 levels. These findings confirmthe role of PAPP-A and IGF-1 in preeclampsia. Both of these hormones have potential as indicatorsand markers for the prediction and management of preeclampsy in early and late onset periods.

Adverse pregnancy outcome in low PAPP-A levels: First trimester screening hospital based study

To assess the adverse pregnancy outcome in Low Pregnancy Associated Plasma Protein -A (PAPP-A) levels in serum.This is a prospective cohort study, which included 2150 pregnant women who attended the antenatal clinic of Obstetrics and Gynecology in the Lok Nayak Hospital, New Delhi, India. Blood samples were collected by the venipuncture method for First trimester screening to assess free β-hCG and PAPP-A concentrations were measured by Auto DELFIA (Perkin Elmer, Turku, Finland).In this study a total of 210 women who have the low PAPP-A value less than 0.4 MoM were under the closer surveillance for serious pregnancy outcome. 33(15.6%) women had pre-eclempsia, 27 (12.9%) cases showed intra-utrine growth retardation (IUGR), 6 (3.0%) cases have intra-utrine death. 48 (22.8%) women have pregnancy induced hypertension, and 96(45.6%) cases have other pregnancy related complication. Low PAPP-A levels gives an indication of adverse pregnancy outcome in the early gestation age during the first trimester.

Pregnancy-Associated Plasma Protein-A: Its Significance as a Single Biomarker for Adverse Obstetric Outcomes

OBJECTIVES: Low levels of pregnancy-associated plasma protein-A in pregnant women linked to unhealthy placentation and a spectrum of maternal and fetal complications. Its assessment as a single biomarker has the potential to identify high-risk pregnancies. This prospective observational study was conducted to find a correlation between low pregnancy-associated plasma protein-A levels in the first trimester of pregnancy with various obstetric outcomes to establish if it can be used as a single biomarker for counseling couples. STUDY DESIGN: The study was conducted at Base Hospital, Delhi Cantt. Maternal serum pregnancy-associated plasma protein-A levels were assessed at 11 to 13+6 weeks of gestation, converted in multiples of the median and patients were followed till delivery. Maternal outcomes were recorded in terms of abortions, development of gestational hypertension, gestational diabetes, preeclampsia, placental abruption, fetal growth restriction, fetal demise, neonatal intensive care unit admission, etc., and analyzed to find an association with levels first trimester of pregnancy-associated plasma protein-A. RESULTS: Low pregnancy-associated plasma protein-A levels showed a statistically significant association with gestational hypertension, preeclampsia, abortion, fetal demise, and also for adverse neonatal outcomes like APGAR <5 at 1 min, fetal growth restriction, neonatal intensive care unit admission, and perinatal deaths. No significant association was observed for preterm delivery, gestational diabetes, and placental abruption. CONCLUSION: Serum pregnancy-associated plasma protein-A levels in the first trimester of pregnancy have the potential of being utilized as a validated marker for adverse pregnancy outcomes. Early identification of such pregnancies can help in optimizing feto-maternal outcomes through closer surveillance, timely intervention, and referral to tertiary care centers. Further research would help the fraternity in developing a prediction model.

Role of First Trimester Screening Biochemical Markers to Predict Hypertensive Pregnancy Disorders and SGA Neonates-A Narrative Review.

Early recognition of high-risk pregnancies through biochemical markers may promote antenatal surveillance, resulting in improved pregnancy outcomes. The goal of this study is to evaluate the possibilities of using biochemical markers during the first trimester of pregnancy in the prediction of hypertensive pregnancy disorders (HPD) and the delivery of small-for-gestational-age (SGA) neonates. A comprehensive search was conducted on key databases, including PubMed, Scopus, and Web of Science, for articles relating to the use of biochemical markers in the prediction of HPD and SGA. The findings show that changes in the levels of biomarkers in the early pregnancy phases could be an important indicator of adverse pregnancy outcomes. The literature shows that low PAPP-A (pregnancy-associated plasma protein A) and PlGF (placental growth factor) levels, low alkaline phosphatase (AP), higher sFlt-1 (soluble fms-like Tyrosine Kinase-1) levels, higher AFP (alfa fetoprotein) levels, and elevated levels of inflammatory markers such as β-HGC (free beta human chorionic gonadotropin), interferon-gamma (INF-γ), and tumor necrosis factor-α (TNF-α) may be associated with risks including the onset of HPD, fetal growth restriction (FGR), and delivery of SGA neonates. Comparatively, PAPP-A and PlGF appear to be the most important biochemical markers for the prediction of SGA and HPD.

Correlation Between PAPP-A Levels Determined During the First Trimester and Birth Weight at Full-Term.

Foetal birth weight is an important determinant of perinatal health. For this reason, various methods have been investigated for estimating this weight during pregnancy. The aim of this study is to evaluate the possible relationship between full-term birth weight and pregnancy-associated plasma protein-A (PAPP-A) levels determined during the first trimester as part of combined screening for aneuploidy carried out in pregnant women. We carried out a single-centre study including pregnant women who were being followed up by the Obstetrics Service Care Units of the XXI de Santiago de Compostela e Barbanza Foundation, who gave birth from March 1, 2015, to March 1, 2017, and who had undergone their first-trimester combined chromosomopathy screening. The sample included a total of 2794 women. We found a significant correlation between MoM PAPP-A and foetal birth weight. When MoM PAPP-A was measured at extremely low levels (< 0.3) during the first trimester, the OR for giving birth to a foetus with weight < p10, adjusting for gestational age and sex, was 2.74. For low levels of MoM PAPP-A (0.3-0.44), the OR was 1.52. With regard to the value of MOM PAPP-A levels as a predictor of foetal macrosomia, a correlation could be observed with elevated levels, although this was not statistically significant. PAPP-A determined during the first trimester acts as a predictor of foetal weight at term as well as for foetal growth disorders.

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.

Evaluation of the Relationship between Pregnancy-Associated Plasma Protein A (PAPP-A) and Pregnancy Outcomes.

In the current study, we aimed to evaluate the association between pregnancy-related plasma protein-A (PAPP-A) levels measured in the first trimester and pregnancy outcomes. This is a descriptive-analytical study that was performed in 2019--2021 on 1061 pregnant women in their first trimester. Demographic and basic information of all women were collected. These data included age, weight, parity, and date of delivery. Then the quantity of PAPP-A was recorded in three groups including less than 0.5 MOM, 0.5 to 2.5 MOM, and more than 2.5 MOM. Data of 1061 women were analyzed. 900 women (84.8%) had term delivery and 155 women (14.6%) had pre-term deliveries. PAPP-A levels were normal in 83.4% of women. BMI and number of pregnancies had significant relationships with PAPP-A (p < 0.001, P = 0.03 respectively). The mean BMI in mothers with PAPP-A higher than 2.5 was significantly more than mothers with normal or lower PAPP-A levels (26.2 ± 31, P = 0.04). The frequency of term labor in mothers with normal PAPP-A was higher than other mothers (86.3%, P = 0.04). The frequency of preeclampsia in recent pregnancies in mothers with normal PAPP-A was significantly lower than other mothers (p < 0.001) and the frequency of abortions in recent pregnancies in mothers with PAPP-A less than 0.5 was significantly higher than mothers with normal or elevated PAPP-A (p < 0.001). Mothers with low PAPP-A levels are more likely to have poor pregnancy outcomes such as abortion, pre-term labor, and preeclampsia.

Prediction of spontaneous preterm birth and preterm prelabor rupture of membranes using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks.

To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB. This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs). A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively. We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal serum pregnancy-associated plasma protein-A concentration at 11–14 weeks of gestation and preeclampsia risk of women with common congenital anatomic uterine abnormalities

To evaluate maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels at 11–14 weeks of gestation and preeclampsia risk in women with common congenital anatomic uterine abnormalities (AUAs). First trimester screening markers were compared between 12 AUA pregnancies, 60 age matched controls and 12 cases of early preeclampsia. PAPP-A level and birth weight were significantly lower in AUA compared to control and early preeclampsia group (p<.001). Preeclampsia was absent in the AUAs pregnancies group. Birth weight were similar in AUA group when we compared AUA and control group regarding weeks of gestation at delivery and lower but not significantly, when we compared AUA and early preeclampsia group. Our findings suggest that AUA pregnancies are associated with low first trimester maternal serum PAPP-A concentrations not predictive of susceptibility to preeclampsia. Impact statement What is already known on this subject? During first trimester screening for preeclampsia based on maternal pregnancy-associated plasma protein A (PAPP-A) levels, various parameters are used, such as the somatometric characteristics of pregnant woman, single or multiple pregnancy, smoking status, family history, diabetes, hypertension and measurement of blood pressure and uterine artery Dopplers. What do the results of this study add? Our pioneer study revealed that there is drastic difference in PAPP-A concentration in women with common anatomic uterine abnormalities (AUAs), in comparison with their age matched control women with normal uterus. What are the implications of these findings for clinical practice and further research? Based on our results, uterine anatomical deviations, is another factor which must be taken in account for preeclampsia risk calculation and further clinical consultation and follow up in those pregnancies. Lower PAPP-A levels in AUA cases is a weak predictor of susceptibility to preeclampsia and could be associated to smaller placental size rather than poor placentation and in future research the calculation of the uterine cavity functional dimension may lead to a more accurate clinical assessment.

A prospective cohort study on association of first-trimester serum biomarkers and risk of isolated foetal congenital heart defects

Background This study aims to assess the association between first-trimester biomarkers in foetuses with a non-chromosomal congenital heart defect (CHD) and compares it to the matched healthy foetuses. Method Nuchal Translucency (NT), Pregnancy-Associated Plasma Protein-A (PAPP-A) and free beta-human Chorionic Gonadotropin (β-hCG) were evaluated in 56 isolated foetal heart defects and 224 controls. The CHDs were further divided into Critical CHD (C-CHD) and Non-critical CHD (N-CHD) groups. Results The multiple of the median (MoM) values for PAPP-A were significantly lower (0.87 MoM vs. 0.92 MoM; p = 0.008) in the total CHD group than in controls. The median of foetal NT values was significantly higher in the total CHDs than in controls (1.16 MoM vs. 1.03 MoM; p < 0.001), especially for C-CHDs (1.28 MoM; P < 0.001). There were no significant differences in terms of PAPP-A (p = 0.779) and foetal NT values (p = 0.760) between the N-CHDs and control groups. There were no significant differences within the groups based on free β-hCG, except for a lower β-hCG in C-CHD group than in the control group (0.95 MoM vs. 1.11 MoM; p = 0.022). Conclusion Lower PAPP-A levels and increased NT thickness were associated with an increased risk of CHDs, especially the critical type of CHDs. Clinical significance Maternal serum PAPP-A, measured in the first trimester, is significantly lower in CHD. Foetal NT is significantly thicker in foetuses with CHD, especially those with critical CHD. Maternal serum β-hCG was only decreased among critical CHD group.

The Relationship between the Level of Pregnancy-Associated Plasma Protein A and Placenta Size and Thickness

Background: The low level of pregnancy-associated plasma protein A (PAPP-A) has a relationship with unfavorable outcomes in neonates. This study aimed to evaluate the association between the thickness and size of the placenta in singleton pregnant women. Materials and Methods: In this prospective cohort study, 102 women were investigated in 18-23 weeks and PAPP-A level at the gestational age in 11-14 weeks with a singleton pregnancy who referred to Al-Zahra Hospital, Rasht, Iran, between 2017 and 2018. Serum PAPP-A of pregnant women was measured in the first trimester of pregnancy. Patients who had PAPP-A ≤ 0.5 Multiple of the Median (MOM (were dedicated to an exposed group and others to a non-exposed group. Placental thickness and size were assessed during the second trimester by ultrasound examination and described as abnormal high thickness if the thickness was > 4 cm or more than 50% of the placental length and abnormally small size when the maximum length was < 10 cm. Then, placental thickness and size were compared between the two groups. Results: PAPP-A levels of > 0.5 and ≤ 0.5 were recorded in 60 and 34 patients, respectively. Women with low levels of PAPP-A in the first trimester had an increased incidence of abnormal placental thickness in 13 cases and small placental size in 7 cases, whereas this number was 12 and 7 cases, respectively, in the other group (P = 0.023). The sensitivity and specificity of PAPP-A < 0.55 were 72.3 and 56% for abnormal placental thickness, respectively; the sensitivity and specificity of PAPP-A < 0.55 were 69.3 and 57.1%, respectively, in the assessment of abnormal placenta size. Conclusion Based on the results, the size and thicknesses of the placenta were abnormal in women with a low level of PAPP-A (≤ 0.5).

Role of pregnancy-associated plasma protein A (PAPP-A) and human-derived chorionic gonadotrophic hormone (free β-hCG) serum levels as a marker in predicting of Small for gestational age (SGA): A cohort study.

Background:Small-for-gestational-age (SGA) is one of the most important conditions, which is associated with the risk of perinatal mortality and morbidity. The levels of pregnancy-associated plasma protein A (PAPP-A) and β-human-derived chorionic gonadotrophic (β-hCG) in the first trimester can predict this adverse outcome, considering the controversial nature of studies in this area, this cohort study was conducted to investigate the role of PAPP-A and freeβ-hCG levels for predicting SGA.Materials and Methods:In this cohort study, from 16 randomly selected health centers in Isfahan, Iran, 4605 volunteer pregnant women who had performed first-trimester fetal anomalies screening tests were chosen based on the census, from July 2016 to June 2018. The multiples of the median (MoM) PAPP-A <0.4 and MoM β-hCG >3 were considered as abnormal; the samples were followed up after childbirth. The biomarkers' serum levels, relative risk, and odds ratio (OR) of SGA were compared in both SGA and appropriate for gestational age (AGA) groups.Results:In the SGA group, the mean of MOM PAPP-A was significantly lower (0.96 vs. 1.1 with P = 0.001) and MoM βhCG was significantly higher (1.24 vs. 1.15 with P = 0.01) than the AGA group. Odds for SGA in subjects with MoM PAPP-A <0.4 were 3.213; P = 0.001 and for subjects with MoM βhCG >3 reported as 0.683; P = 0.111.Conclusion:The results of the study showed that the low levels of PAPP-A would cause 3.213 times increase in the chance of developing SGA and no association between high level of βhCG >3 with SGA. Therefore, low level of the PAPP-A is a warning indicator for SGA.

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.

First-trimester maternal serum biomarkers and the risk of cerebral palsy.

To investigate whether combined first-trimester screening (cFTS) biomarkers are associated with cerebral palsy (CP) and to identify CP characteristics associated with abnormal biomarker levels. In this retrospective case-control data linkage study, we matched mothers of 435 singletons with CP from a population register to their cFTS records and selected 10 singleton pregnancy controls per case. We compared mean and abnormal levels (expressed as multiples of the median [MoMs]) of pregnancy-associated plasma protein-A (PAPP-A), beta subunit of human chorionic gonadotrophin (β-hCG), and nuchal translucency between cases and controls and between CP subgroups. Compared with control pregnancies, CP pregnancies had lower mean levels of PAPP-A (0.95 vs 1.01 MoM, p=0.02) and β-hCG (0.93 vs 0.99 MoM, p=0.02). Biomarker levels in CP pregnancies were 1.8 times more likely to be associated with abnormally low levels of PAPP-A (p<0.01), 1.4 times for β-hCG (p=0.12), and 2.6 times for low PAPP-A and β-hCG together (p=0.04). In cases with CP, an abnormally low PAPP-A level was associated with moderate preterm birth, low Apgar scores, and Gross Motor Function Classification System level V. Low β-hCG was associated with very low birthweight. Low first-trimester biomarker levels suggest a role for early pregnancy factors in some causal pathways to CP. Low first-trimester levels of biomarkers in maternal serum are associated with later cerebral palsy (CP). Early pregnancy factors have potential importance in causal pathways to CP. Causal pathways involving preterm birth, term neonatal encephalopathy, and genetic syndromes may be implicated.

Abstract 16738: Association Between First and Second Trimester Maternal Screening Biochemistry, Ultrasound, and Fetal Brain Growth in Presence of Fetal or Maternal Congenital Heart Disease

Introduction: Newer research has highlighted significant neurological impairments in children and adults with congenital heart disease (CHD). The more severe the heart defect, the higher the neurologic impairment. Pregnancies complicated by fetal or maternal CHD carry a higher risk of placental abnormalities. We studied the association between pregnancy hormonal levels and fetal head and body growth. Hypothesis: Placental dysfunction in pregnancies with fetal or maternal CHD alters pregnancy hormonal levels affecting fetal brain and somatic growth. Methods: We performed a retrospective case-control study on pregnant women (year 2010-2019) at the University of Iowa. Only women with first and/or second trimester prenatal screening (ultrasound and blood test) were included. Pregnancies with fetal chromosomal abnormalities, multiple gestation, maternal diabetes, smoking, or hypertension were excluded. Pregnancies were either healthy controls (n=36), women with CHD (MCHD; n=26), or fetus with CHD (FCHD; n=23). Pregnancy hormonal levels, ultrasound findings, and fetal/neonatal growth percentiles and/or z-scores data were analyzed. Results: Women with CHD were younger (p=0.004) with increased fetal nuchal translucency (p=0.003) compared to controls. Women in MCHD (p=0.02) and FCHD (p=0.02) group delivered earlier than controls. FCHD had significantly lower pregnancy associated plasma protein-A (PAPP-A) levels than controls (p=0.04). The groups had no difference in the second trimester fetal head circumference (HC) and femur length. FCHD group had significantly smaller HC percentile (p=0.03) and z-scores (p=0.03) at birth than controls. Both FCHD and MCHD had smaller birth weight and length compared to controls. However, only FCHD group demonstrated significantly lower HC to birth weight ratio (p=0.01). The controls had a positive correlation between human chorionic gonadotropin level and head circumference z-score at birth (r=0.34;p=0.053). Conclusions: Pregnant women with CHD have increased fetal nuchal translucency and deliver at earlier gestational age. Women with fetal CHD have smaller neonatal head and body size at birth with associated low PAPP-A level early in their pregnancy probably related to placental dysfunction.

The effect of maternal alcohol and drug abuse on first trimester screening analytes: a retrospective cohort study

BackgroundThe purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use.MethodsA routine combined FTS including measurements of maternal serum levels of free β-human chorionic gonadotropin subunit (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9–11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11–13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed.ResultsFree β-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free β-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups.ConclusionsThe present study shows increased free β-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free β-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.

High Frequency of Fetal Loss in Fetuses with Normal Karyotype and Nuchal Translucency ≥ 3 among the Iranian Pregnant Women

Objective: The purpose of this study was comparison of association of three main first trimester screening factors with pregnancy outcomes among Iranian pregnant women. Materials and methods: This prospective study was done during 2017-2019 years in Qazvin, Iran. To do so, a total of 1500pregnant women in first trimester were enrolled. At the first step, Nuchal translucency (NT) was measured in 11-13 ± 5 week, then the serum pregnancy-associated plasma protein A (PAPP-A) and free-β-human chorionic gonadotropin (free-β-HCG) were measured in 12-14 weeks of gestation. Pregnant women were followed up until the end of pregnancy for the complications of pregnancy such as intra-uterine growth retardation (IUGR), intrauterine death (IUFD), different types of fetal loss and preterm labor. Results: The results showed that low levels of serum biomarkers had more association with pregnancy complications in comparison to high levels of them. Significant association of IUGR (P = 0.001), IUFD (P = 0.032) and pre-term labor (P = 0.002) was shown in women with low serum levels of PAPP-A in comparison to low serum levels of free-β-hCG. Significant high frequency of different types of fetal loss (IUFD, Abortion, Elective termination) was shown in fetuses with N ≥ 3 in comparison to low levels of serum biomarkers (P = 0.001). Conclusion: This study highlighted the importance of accurately interpreting the results of the first trimester of pregnancy screening which should be considered by primatologists for subsequent pregnancy care.

Marginal placental cord insertion: the need for follow up?

Objective The objectives of this study were (1) to estimate the association between marginal placental cord insertion (PCI) and small for gestational age (SGA) and other adverse perinatal outcomes and (2) to determine if pregnancy-associated plasma protein A (PAPP-A) levels was altered in these patients. Methods It was a retrospective cohort study of singleton pregnancies undergoing ultrasound between 2016 and 2018. Marginal PCI was defined as a distance of ≤2 cm from placental edge to PCI site, visualized in both sagittal and transverse planes, and diagnosed between 16 and 32 weeks. Velamentous PCI were excluded. The primary outcome was SGA, defined as birthweight below 10th percentile for gestational age. Pregnancies with marginal PCI were compared to those with normal PCI with respect to maternal characteristics, PAPP-A levels and adverse perinatal and delivery outcomes. Results The incidence of marginal PCI was 4.2% (76/1819). Compared to those with a normal PCI, patients with a marginal PCI were more likely to be nulliparous and less likely to be African American or morbidly obese (p < .05). SGA rate was similar between the groups (17.6% vs. 18.1%). There was a trend toward an increased incidence of oligohydramnios, polyhydramnios and breech presentation in patients with marginal PCI; however, these did not reach statistical significance. The incidence of low PAPP-A level was comparable between the groups (18.4% vs. 14.3%, p > .05). Conclusion Our study did not demonstrate any increase in adverse pregnancy outcomes in the presence of marginal PCI. These findings may provide reassurance for counseling patients with this sonographic finding.

Low First Trimester Pregnancy-Associated Plasma Protein-A Levels Are Not Associated with an Increased Risk of Intrapartum Fetal Compromise or Adverse Neonatal Outcomes: A Retrospective Cohort Study.

The aim of this study was to assess if women with a low first trimester maternal pregnancy-associated plasma protein-A (PAPP-A) level are at increased risk of emergency cesarean (EmCS) for intrapartum fetal compromise (IFC) and/or adverse neonatal outcomes. This was a retrospective cohort study performed at Mater Mother’s Hospital, Brisbane, Australia, between 2016 and 2018. All women with a singleton, euploid, non-anomalous fetus with a documented PAPP-A level measured between 10 +0 and 13 +6 weeks gestation during the study period were included. Data were extracted from the institution’s perinatal database and dichotomized according to PAPP-A level (≤0.4 Multiples of Medium (MoM) vs. >0.4 MoM). The primary outcomes were EmCS-IFC and a composite of severe adverse neonatal outcomes (SCNO). Nine thousand sixty-one pregnancies were included, 3.3% with a PAPP-A ≤ 0.4 MoM. Low maternal PAPP-A was not associated with an increased risk of EmCS-IFC (adjusted odds ratio (aOR) 0.77, 95% confidence interval (CI) 0.24–2.46, p = 0.66) or SCNO (aOR 0.65, 95% CI 0.39–1.07, p = 0.09). Low PAPP-A was associated with increased odds of pre-eclampsia, preterm birth and birthweight < 10th centile. In conclusion, low maternal PAPP-A level is not associated with an increased risk of EmCS IFC or adverse neonatal outcomes despite greater odds of low-birthweight infants and preterm birth.