UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

OBJECTIVE: The first trimester combined risk of trisomy 21 is obtained by multiplying the risk related to maternal age by the likelihood ratios of nuchal translucency, free beta-human chorionic gonadotrophin (β-hCG) and placenta associated plasma protein-A. Beyond five multiples of the median (MoM) of β-hCG, the risk of trisomy 21 is truncated. The objective of the present study was to evaluate the evolution of the first trimester combined risk of trisomy 21 in individuals with first-trimester free-β-hCG levels between 5 and 10 MoM.
METHODS: We conducted a non-interventional cohort study from a 6-year database of combined first-trimester trisomy 21 screening of all individuals who underwent the screening in a French specialized medical analysis center. We included all pregnant individuals who had a serum-free β-hCG between 5 and 10 MoM. Patients for whom the status of the fetus, with or without trisomy 21, was not identified by the outcome of the pregnancy or by a karyotype result were excluded from the study. The discriminatory capacity of free-β-hCG above 5 MoM was studied by a receiver operating characteristic curve. We used an orthogonal polynomial regression to represent the evolution of likelihood ratios according to free-β-hCG in MoM.
RESULTS: Among 413 216 combined first-trimester screens of trisomy 21, 2239 (0.5%) screens met the inclusion criteria. In the selected population, 801 (35.8%) were excluded from the study because of missing fetal or neonatal status, and 46 (3.2%) fetuses out of 1438 included were diagnosed with trisomy 21. For free β-hCG values between 5 and 10 MoM, the area under the curve is 0.56 (0.46-0.65). The scatterplot of the likelihood ratio of β-hCG showed an increasing parabolic pattern: the likelihood of trisomy 21 increases with the free-β-hCG threshold.
CONCLUSIONS: To override the truncated risk of trisomy 21 in case of free β-hCG values between 5 and 10 MoM, the study has allowed us to estimate the adjusted risk of trisomy 21, enabling health professionals to offer appropriate prenatal counseling.

OBJECTIVE: Calcific aortic stenosis (AS) is the most common form of calcific aortic valve disease. Many matrix metalloproteinase (MMP) have been shown to be expressed in aortic sclerosis and contribute to valve fibrosis and calcification. We investigated the relationship between Pregnancy-Associated Plasma Protein-A (PAPP-A) and AS.
METHODS: Sixty-one patients who referred to our cardiology clinic having AS diagnosed with transthoracic echocardiography and thirty control subjects were included in this study. The patient group was divided into two groups as mild and moderate-severe AS in terms of echocardiography results. Levels of C-reactive protein (CRP), insulin-like growth factor-1 (IGF-1) and PAPP-A were measured.
RESULTS: There was statistically significant difference between the patient and control group for PAPP-A (p = 0.009). In addition, the difference between MPV, IGF-1 and PAPP-A levels of control and AS groups was found. We found that serum PAPP-A level was an independent predictor of AS (B = 0.107, p = 0.01) by logistic regression analysis. In linear regression analysis, a significant correlation was found for AS severity with MPV, IGF-1 and PAPP-A levels, respectively (p = 0.025, p = 0.004, p = 0.035). It was revealed that PAPP-A and IGF-1 were negatively correlated (r = -0.327, p = 0.002). Correlation of serum PAPP-A level with echocardiographic parameters was no observed.
CONCLUSIONS: The level of PAPP-A may be a marker used in diagnosis rather than a marker used to determine the severity of AS. Studies with larger patient populations may further explain the role of PAPP-A in the diagnosis and treatment of AS.

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

Breast cancer is the most common malignancy in women. Noninvasive biomarkers are needed for its early diagnosis and/or prognosis.
The aim of this case-control study was the comparison of serum activins, follistatins, and members of the IGF family levels in women with benign vs malignant breast neoplasms vs apparently healthy controls.
Women with breast benign (n = 100) or malignant tumors (n = 145) and disease-free controls (n = 100) were recruited. Women with breast cancer were subsequently subdivided into recently diagnosed/treatment-naive (n = 112) and chemotherapy-treated (n = 33). Anthropometric, demographic, biochemical, and histological data were recorded.
A breast cancer clinic in Thessaloniki, Greece.
Serum levels of activin A, activin B, follistatin, follistatin-like (FSTL)-3, total IGF-1, total and intact insulin-like growth factor binding protein (IGFBP)-4 and pregnancy-associated plasma protein-A (PAPP-A) were measured with highly specific ELISA kits.
In adjusted comparisons, substantial differences in FSTL-3, total and intact IGFBP-4, PAPP-A, and total IGF-1 were observed between groups. In logistic regression analysis, primarily total IGFBP-4 levels were independently associated with the overall presence of breast malignancy. FSTL-3 was the only variable that could distinguish between a benign vs malignant breast mass. In linear regression analysis, FSTL-3 was independently associated with tumor size.
We showed that members of the IGF-1/IGFBP-4/PAPP-A axis and FSTL-3 may serve as surrogate markers in breast cancer. Future mechanistic and longitudinal studies and/or clinical trials are needed to explore the efficacy of these molecules as noninvasive biomarkers and their possible therapeutic potential in breast cancer.

暂无摘要。

OBJECTIVE: To 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.
METHODS: Clinical 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).
CONCLUSIONS: Serum 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.

OBJECTIVE: To evaluate the levels of peripheral blood CD34+ cells in women who subsequently had a spontaneous miscarriage (SM).
METHODS: We enrolled 11 women who had SM, matching them for age, BMI and gestational age with 33 healthy pregnancies (controls). From a blood sample at 9th-11th weeks of pregnancy, we evaluated PAPP-A, free β-hCG, T (suppressor and helper), NK, B, CD34+ cells.
RESULTS: In peripheral blood of women who had SM, PAPP-A and CD34+ cells were significantly lower (p < 0.001) compared to control group.
CONCLUSIONS: CD34+ cell low level in peripheral blood is associated with increased risk of SM.

To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors.
Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls.
Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis < 37 weeks of gestation) and 13 of them had early-onset pre-eclampsia (diagnosis < 34 weeks of gestation). They had lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (%hCG-h) than controls. In receiver-operating characteristics (ROC) curve analysis, the area under the curve (AUC) for the combination of PlGF, PAPP-A, %hCG-h, nulliparity and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699-0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750-0.988) for early-onset pre-eclampsia. Without %hCG-h the AUC values were 0.756 (95% CI 0.651-0.861) and 0.810 (95% CI 0.682-0.938) respectively. For prediction of gestational hypertension, the AUC for %hCG-h was 0.708 (95% CI 0.608-0.808), but for other markers the AUC values were not significant. None of the AUC values were significant for the prediction of SGA infants in normotensive women.
First trimester maternal serum %hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors.

Increased nuchal translucency (NT) thickness is present in 40% of fetuses with diaphragmatic hernia, including 80% of those that result in neonatal death and in 20% of the survivors. A 33-year-old nulliparous woman had first trimester scan at 12 weeks. The fetus had a NT of 2.3 mm, normal ductus venosus (DV), and tricuspid doppler and present nasal bone. Pregnancy-associated plasma protein A (PAPP-A) was 0.59 MoM and beta-human chorionic gonadotropin (b-hCG) 2.56 MoM. The couple did not opt for chorionic villous sampling (CVS) and repeat ultrasound examination was advised. At 18 weeks, ultrasound revealed left sided diaphragmatic hernia. The couple consented for termination of the pregnancy. The molecular test showed normal karyotype and male gender. In such cases with intrathoracic herniation of abdominal viscera, the increased NT may be the consequence of venous congestion due to mediastinal compression. The prolonged compression of the lungs causes pulmonary hypoplasia. Increased NT with normal fetal karyotype is associated with structural fetal anomalies like diaphragmatic hernia and screening at 16-18 weeks is imperative.