Trimester Pregnancy-associated Plasma Protein Research Articles

First and second trimester maternal serum markers for prenatal aneuploidy screening: An update on the adjustment factors for race, smoking, and insulin dependent diabetes mellitus

ObjectivesThe concentrations of maternal serum markers for aneuploidy screening are influenced by maternal characteristics such as race, smoking, insulin dependent diabetes mellitus (IDDM), and in vitro fertilization (IVF). Accurate risk estimation requires adjustment of initial values for these characteristics. This study aims to update and validate adjustment factors for race, smoking, and IDDM. MethodsThe study included singleton pregnancies that received multiple marker screening in Ontario, Canada between January 2012, and December 2018, and had their information collected in the Better Outcomes Registry & Network (BORN) Ontario. Serum markers assessed included first trimester pregnancy-associated plasma protein A (PAPP-A), free β and total human chorionic gonadotropin (hCG), placental growth factor (PlGF) and αlpha-fetoprotein (AFP); second trimester AFP, unconjugated estriol (uE3), total hCG and inhibin A. The Mann-Whitney U test was used to assess the differences in the median multiple of the median (MoM) of serum markers between study and reference groups. New adjustment factors were generated by dividing the median MoM of a particular race, individuals who smoke tobacco, or have IDDM by those of the reference groups. ResultsThe study included 624,789 pregnancies. There were statistically significant differences in serum marker concentrations among pregnant individuals who were Black, Asian, or First Nations compared to a White group, those who smoked compared to Non-smoking individuals, and those with IDDM compared to Non-IDDM group. New adjustment factors for race, smoking, and IDDM were validated by comparing median MoM of serum markers corrected using the current adjustment factors and new adjustment factors generated in this study. ConclusionThe adjustment factors generated in this study can adjust the effects of race, smoking, and IDDM on serum markers more accurately.

Early pregnancy prediction of gestational diabetes mellitus risk using prenatal screening biomarkers in nulliparous women

AimsTo evaluate the clinical utility of first and second trimester prenatal screening biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM) risk in nulliparous women. MethodsWe conducted a population-based cohort study of nulliparous women participating in the California Prenatal Screening Program from 2009 to 2011 (n = 105,379). GDM was ascertained from hospital discharge records or birth certificates. Models including maternal characteristics and prenatal screening biomarkers were developed and validated. Risk stratification and reclassification were performed to assess clinical utility of the biomarkers. ResultsDecreased levels of first trimester pregnancy-associated plasma protein A (PAPP-A) and increased levels of second trimester unconjugated estriol (uE3) and dimeric inhibin A (INH) were associated with GDM. The addition of PAPP-A only and PAPP-A, uE3, and INH to maternal characteristics resulted in small, yet significant, increases in area under the receiver operating characteristic curve (AUC) (maternal characteristics only: AUC 0.714 (95% CI 0.703–0.724), maternal characteristics + PAPP-A: AUC 0.718 (95% CI 0.707–0.728), maternal characteristics + PAPP-A, uE3, and INH: AUC 0.722 (0.712–0.733)); however, no net improvement in classification was observed. ConclusionsPAPP-A, uE3, and INH have limited clinical utility for prediction of GDM risk in nulliparous women. Utility of other readily accessible clinical biomarkers in predicting GDM risk warrants further investigation.

Gestational diabetes mellitus and first trimester pregnancy-associated plasma protein A: A case-control study in a Chinese population.

Aims/IntroductionTo investigate the relationship between pregnancy‐associated plasma protein A (PAPP‐A) and gestational diabetes mellitus (GDM), and to determine whether PAPP‐A has improved value for predicting GDM in a Chinese population.Materials and MethodsClinical data for 599 GDM patients and 986 unaffected pregnant women undergoing both antenatal examinations and delivery were retrospectively analyzed. First‐trimester serum PAPP‐A levels were compared between the groups. Binary logistic regression analysis was used to explore the risk factors for GDM, and the area under the receiver operating characteristic curve was used to determine the value of PAPP‐A for predicting GDM.Results GDM‐affected and unaffected pregnant women were significantly different in terms of age (P < 0.001), BMI (P < 0.001), family history of diabetes (P = 0.002), α‐thalassemia trait (P < 0.01), parity (P < 0.001), conception methods (P < 0.001), gestational weeks at the time of labor (P < 0.001) and corrected PAPP‐A multiples of the median values (P < 0.001). Binary logistic regression analysis showed that PAPP‐A levels were negatively related to the subsequent development of GDM (odds ratio 0.798, 95% confidence interval 0.647–0.984). The area under the receiver operating characteristic curve for maternal factors was 0.684 (95% CI: 0.657–0.711), and did not significantly differ from that for the combination of maternal factors and serum PAPP‐A levels, which was 0.686 (95% CI: 0.660–0.713; χ2 = 0.625, P = 0.429).ConclusionsSerum PAPP‐A was an independent factor for the development of GDM in pregnant Chinese women. Serum‐PAPP‐A does not have improved value with respect to predicting GDM when combined with other maternal factors.

Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

Association of low levels of first trimester Pregnancy Associated Plasma Protein (PAPP-A) with adverse pregnancy outcomes: An observational study

Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma Protein A and Total Human Chorionic Gonadotropin (Podcast)

Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma Protein A and Total Human Chorionic Gonadotropin (Podcast)

Early-onset severe preeclampsia by first trimester pregnancy-associated plasma protein A and total human chorionic gonadotropin.

This study aims to evaluate the relationship between early-onset severe preeclampsia and first trimester serum levels of pregnancy-associated plasma protein A (PAPP-A) and total human chorionic gonadotropin (hCG). The association between early-onset severe preeclampsia and abnormal levels of first trimester PAPP-A and total hCG in maternal serum were measured in a sample of singleton pregnancies without chromosomal defects that had integrated prenatal serum screening in 2009 and 2010 (n = 129,488). Logistic binomial regression was used to estimate the relative risk (RR) of early-onset severe preeclampsia in pregnancies with abnormal levels of first trimester PAPP-A or total hCG as compared with controls. Regardless of parity, women with low first trimester PAPP-A or high total hCG were at increased risk for early-onset severe preeclampsia. Women with low PAPP-A (multiple of the median [MoM] ≤ the 10th percentile in nulliparous or ≤ the 5th percentile in multiparous) or high total hCG (MoM ≥ the 90th percentile in nulliparous or ≥ the 95th percentile in multiparous) were at more than a threefold increased risk for early-onset severe preeclampsia (RR, 4.2; 95% confidence interval [CI], 3.0-5.9 and RR, 3.3; 95% CI, 2.1-5.2, respectively). Routinely collected first trimester measurements of PAPP-A and total hCG provide unique risk information for early-onset severe preeclampsia.

First trimester pregnancy-associated plasma protein A and human chorionic gonadotropin-beta in early and late pre-eclampsia

The aim of this study was to compare pregnancy-associated plasma protein A (PAPP-A) and the β-subunit of human chorionic gonadotropin (hCGβ) measured in maternal plasma at the first trimester screening, in women who later developed early or late pre-eclampsia (PE) to women with normal pregnancies. In the study were included 161 cases with PE and 88 controls with uncomplicated pregnancies. Plasma PAPP-A and hCGβ were measured between gestational age (GA) 8+2 and 14+0, and cases with early and late onset PE were compared with controls. Median of hCGβ (MoM) was lower in women with early (p<0.05) and late PE (p<0.05) compared to healthy pregnant women. Median (range) of hCGβ (MoM) for women with early onset PE, late onset PE, and women with healthy pregnancies, were 0.75 (0.30-1.21), 0.93 (0.26-3.18), and 0.97 (0.33-4.12), respectively. No significant difference in the median of PAPP-A (MoM) was found between the groups. hCGβ was significantly lower in pregnancies that subsequently developed PE and might be of use in the effort of trying to find ways to predict PE. No significant difference was found for PAPP-A in our study.

269: Association between severe early onset preeclampsia (PE) and serum measures of first trimester pregnancy associated plasma protein A (PAPP-A) and human chorionic gonadotrophin (hCG)

STUDY DESIGN: Human placental BP and CV samples were obtained from singleton pregnancies (24-41 weeks gestation). PE samples (n1⁄48) were gestational-age matched to CTL (n1⁄48). Term CTL samples were used for the labor (n1⁄48) and non-labor (n1⁄48) samples. Tissues were dissected, rinsed and frozen after delivery (<60 min). Immunoblot analysis was performed on protein lysates with anti-PAPP-A2 (RD 1:1,000) or anti-b-actin antibody (Sigma; 1:2000) to normalize for protein loading. Densitometry of the immunoreactive bands was performed using Biorad Chemi Doc. Statistical analysis was performed using Prism 5.0 to compare means (t-test) and determine correlations (Pearson). A p-value of <0.05 was considered significant. RESULTS: PAPPA-A2 levels were significantly higher in PE compared to CTL in both the BP (p1⁄40.02) and CV (p1⁄40.003). Evaluation of preterm and term samples separately maintained significant differences for preterm BP (p1⁄40.004), preterm CV (p1⁄40.03) and term CV (p1⁄40.005); but not for term BP (p1⁄4 0.37). PAPP-A2 expression was not affected by labor in the BP (p1⁄4 0.22) or CV (p1⁄4 0.28). PAPP-A2 levels showed strong correlation between BP and CV in CTL labor (r1⁄4 0.89, p1⁄40.003) and non-labor samples (r1⁄4 0.73, p1⁄4 0.04). In contrast, a non-significant weak inverse correlation between BP and CV PAPP-A2 expression was noted for PE samples (r1⁄4 -0.18; p1⁄40.66). CONCLUSION: PAPP-A2 levels in PE are more dysregulated in the CV compared to BP. While PAPP-A2 levels show a strong correlation between BP and CV of CTL placentas, this is not seen in the PE samples also suggesting differential regulation of PAPP-A2 in these regions. Labor does not alter PAPP-A2 expression; thus is not a confounder.

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

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

First trimester PAPP-A MoM values predictive for breech presentation at term of pregnancy

Introduction: Our aim was to state the role of first trimester pregnancy-associated plasma protein A (PAPP-A)-multiple of the median (MoM) value as a predictor for breech presentation at term of pregnancy.Materials and methods: In this retrospective study, we present data for 1100 singleton full-term deliveries that took place in a third-level hospital setting in northeast Italy between January 2004 and July 2007. For each case, PAPP-A, free beta-human chorionic gonadotropin and nuchal translucency were measured during prenatal trisomies screening (between 11 weeks and 13 weeks and 6 d). A wide range of predictive factors for breech presentation at term of pregnancy and other confounding elements were considered.Results: Of the 1100 singleton deliveries at term considered in our study, 40 babies were in breech presentation. Using bivariate analysis and multivariate logistic regression, a lower PAPP-A MoM than 0.63 (first quartile of our distribution) in the first trimester (OR 2.41, CI.95 1.25–4.67), and placental index at term higher than the median value (OR 2.04, CI.95 1.00–4.17) were proven to be associated with breech presentation at term.Conclusions: A low PAPP-A during the first trimester was a predictive factor for breech presentation at term of pregnancy. Acknowledging and acting on this predictor could enable improved management of breech foetuses in the future.

The predictive value of 18 and 22 week uterine artery Doppler in patients with low first trimester maternal serum PAPP‐A

To determine if the addition of uterine artery (UA) Doppler pulsatility index (PI) at 18 and 22 weeks of gestation improves the predictive accuracy of low first trimester pregnancy associated plasma protein A (PAPP-A) in the detection of adverse obstetrical outcomes. This was a prospective interventional study. All women undergoing first trimester combined screening (FTS) at a single center, with a low maternal serum PAPP-A level (<0.4 MoM), were included. Patients underwent bilateral UA Doppler assessments at 18 and 22 weeks of gestation. A positive test was defined as a mean PI > 1.45. Primary outcomes were obtained from chart review, and logistic regression analysis was used to compare outcomes with positive and negative tests. Positive and negative predictive value, specificity and sensitivity were calculated. Between January and October 2007, 5359 women completed FTS. Among the low PAPP-A group (n = 289), 18 week UA Doppler was a significant predictor of low birth weight (OR = 2.28, p = 0.04) while 22 week UA Doppler significantly predicted preterm birth (OR = 12.6, p = 0.001), small for gestational age (OR = 8.24, p = 0.001) and low birth weight (OR = 2.28, p = 0.04). Test characteristics suggested improved positive and negative predictive value for Doppler at 22 versus 18 weeks for these outcomes. UA Doppler at 22 weeks is a useful adjunct in patients with low PAPP-A. However, a negative Doppler does not rule out all adverse outcomes and clinical judgment is advised in the management of these patients.

30: First trimester pregnancy-associated plasma protein A and subsequent abnormalities of fetal growth

30: First trimester pregnancy-associated plasma protein A and subsequent abnormalities of fetal growth