Ioannis Papastefanou

Performance of third-trimester ultrasound for prediction of small-for-gestational-age neonates and evaluation of contingency screening policies

To assess the performance of third‐trimester fetal biometry and fetal Doppler studies for the prediction of small‐for‐gestational‐age (SGA) neonates, and to explore contingency strategies using a first‐trimester prediction model based on maternal and fetal parameters and third‐trimester ultrasound.

Cervical Length Changes From the First to Second Trimester of Pregnancy, and Prediction of Preterm Birth by First-Trimester Sonographic Cervical Measurement

The purpose of this study was to examine the evolution of cervical length from the first to second trimester of pregnancy and the value of first‐trimester cervical measurement in the prediction of preterm delivery.

First trimester prediction of small- and large-for-gestation neonates by an integrated model incorporating ultrasound parameters, biochemical indices and maternal characteristics.

Objective. To identify maternal/pregnancy characteristics, first trimester ultrasound parameters and biochemical indices which are significant independent predictors of small‐for‐gestational age (SGA) and large‐for‐gestational age (LGA) neonates. Design. Retrospective cross‐sectional study. Setting. Two fetal Medicine Units. Population. 4 702 singleton pregnancies presenting for screening for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry at 11–14 weeks. Methods. Reference ranges for birthweight applied to our population were constructed by the Royston and Wright method. Multiple logistic regression was applied to develop first trimester prediction models for SGA and LGA. Main outcome measures. Birth of SGA or LGA neonate. Results. Maternal height, parity, smoking, assisted conception, delta crown–rump length, delta nuchal translucency, free beta human chorionic gonadotrophin and pregnancy‐associated plasma protein‐A were significant independent predictors of SGA. Maternal weight and height, smoking, delta crown–rump length and delta nuchal translucency were significant independent predictors of LGA. Models for SGA (AUC=0.7296, CI: 0.69–0.76, p<0.0001) and LGA (AUC=0.6901, CI: 0.65–0.72, p<0.0001) were derived, applicable to routine obstetric population at low risk for these conditions. For 20% screen positive rate the modeling achieves sensitivities of about 55% for SGA and 48% for LGA neonates. Conclusion. Prediction for birthweight deviations is feasible using data available at the routine 11–14 weeks’ examination. Delta CRL and delta nuchal translucency were significant independent predictors for both SGA and LGA.

Performance of the ultrasound examination in the early and late third trimester for the prediction of birth weight deviations

This study aimed to define the optimal gestational age in the third trimester, early (30–33 weeks + 6 days) versus late (34–37 weeks), for performing an ultrasound examination for fetal biometry to predict birth weight deviations: small for gestational age (SGA ≤ 5th centile) and large for gestational age (LGA ≥ 95th centile) neonates.

Fetal intracranial translucency and cisterna magna at 11 to 14 weeks: reference ranges and correlation with chromosomal abnormalities

To measure the intracranial translucency (IT) and the cisterna magna (CM), to produce reference ranges and to examine the interobserver and intraobserver variability of those measurements. To examine the possible association of IT with chromosomal abnormalities.

Relation between first trimester maternal serum leptin levels and body mass index in normotensive and pre-eclamptic pregnancies--role of leptin as a marker of pre-eclampsia: a prospective case-control study.

Objective. We measured first trimester plasma leptin concentrations in 37 women who subsequently developed pre-eclampsia and 53 normotensive controls to determine the interrelation between leptin and body mass index (BMI) in both groups. We further investigated the association between the risks for pre-eclampsia with maternal leptin levels. Methods. Bloods samples were collected at 13 weeks. Non-parametric tests, Spearmans correlation, linear regression analysis and multiple logistic regression analysis were applied in our data. Results. 1 kg/m2 increase in pre-pregnancy BMI was related to a 2.747 (95% CI: 3.242–2.252) ng/ml rise in leptin concentration among cases and 2.502 (95% CI: 2.873–2.131) ng/ml rise in leptin concentrations among controls. Increased leptin concentration (≥25.3 ng/ml ) in lean women is associated with a 18.8-fold increased risk of pre-eclampsia (adjusted OR: 18.8, CI: 1.8–194, p = 0.014 ). Leptin treated as a continuous variable is a significant predictor of pre-eclampsia (adjusted OR: 1.08, CI: 1.018–1.133, p = 0.009). Conclusion. Increased leptin concentration can definitely contribute to the prediction of pre-eclampsia in lean women, but this is not the case in overweight women. Further research in terms of longitudinal case–control studies is required to clarify the predictive value of pre-eclampsia.

Elevated placental growth factor concentrations at 11–14 weeks of gestation to predict gestational diabetes mellitus

OBJECTIVE To examine maternal serum concentrations of placental growth factor (PlGF) at 11-14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. METHODS Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal-pregnancy characteristics were analyzed. RESULTS Log10 transformed PlGF (log10 PlGF) was not related to maternal factors. Log10 PlGF was increased (p=0.008) in the GDM group compared to the control group. Log10 PlGF was associated with fasting glucose levels (p=0.04) in the oral glucose tolerance test. Log10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group. Maternal weight and maternal age were the only predictors of GDM among the maternal factors [area under the curve (AUC)=0.73, p<0.001]. Log10 PlGF alone was a significant predictor of GDM (AUC=0.63, p<0.001). Combination of maternal weight, maternal age and log10 PlGF resulted in an improved prediction (DR=71.4%, for 25% FPR, AUC=0.78, Model R(2)=0.17, p<0.001). CONCLUSION At 11-14weeks in pregnancies that develop GDM, the maternal serum levels of PlGF are increased. Measurement of serum PlGF at 11-14weeks improves the performance of early screening for GDM provided by maternal factors alone.

Increased Maternal Serum Interleukin-6 Concentrations at 11 to 14 Weeks of Gestation in Low Risk Pregnancies Complicated with Gestational Diabetes Mellitus: Development of a Prediction Model

The aim of the study was to examine interleukin-6 (IL-6) maternal serum concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit. Study population included 40 GDM cases and 94 controls. Maternal characteristics, first trimester ultrasound markers, biochemical indices, and IL-6 levels were used for our analysis. IL-6 was related to maternal weight among the maternal characteristics, (R(2)=0.0679, p=0.01). IL-6 was increased (p=0.001) in the GDM group (median=2 pg/ml) compared to the control group (median=1.5 pg/ml) even after adjustment for maternal weight. IL-6 was inversely related to birth weight adjusted for gestational age at delivery (r=-0.3382, p<0.001) and glucose levels at oral glucose test. Maternal weight and age were the only predictors of GDM among the maternal characteristics [Detection Rate (DR)=59.4%; for 25% False Positive Rate (FPR); Area Under the Curve (AUC)=0.7291; Model R(2)=0.1096, p<0.001]. IL-6 alone was a significant predictor of GDM (DR=51.3%; for 25% FPR; AUC=0.6731; Model R(2)=0.0616, p<0.001). Combination of maternal characteristics with IL-6 yielded an improved prediction (DR=67.5%; for 25% FPR; AUC=0.7586; Model R(2)=0.1521, p<0.001). IL-6 concentrations are increased at 11-14 weeks in pregnancies with GDM. Combination of maternal characteristics and maternal serum IL-6 levels may provide effective first trimester screening for GDM.

A predictive model of short cervix at 20–24 weeks using first-trimester cervical length measurement and maternal history

To develop a model for the prediction of short cervix ( ≤ 15 mm) at 20–24 weeks by combining maternal history and transvaginal ultrasonographic measurement of cervical length at 11–14 weeks. To explore the value of an additional ultrasound examination of the cervix at about 17 weeks.

Correlation between maternal first trimester plasma leptin levels and birth weight among normotensive and preeclamptic women

Objective. To determine the connection between maternal first trimester serum leptin levels and newborn weight. Methods. The study included 37 preeclamptic women and 53 normotensive women who considered the control group. Maternal blood samples were withdrawn at 13 weeks of gestation for the measurement of leptin concentrations. Birth weights were transformed to z-scores according to maternal and obstetrical features, based on customised centiles. Non-parametric tests, students t-test, Pearsons correlation, Spearmans correlation and linear regression analysis were performed in our analysis. Results. Pre-pregnancy body mass index and first trimester maternal plasma leptin levels were significantly higher among women with preeclampsia (p = 0.015 and p < 0.001, respectively). Birth weight z-score was negatively correlated with leptin levels (r = −0.570, p < 0.001), in preeclamptic group and in control group (r = −0.477, p < 0.001). The regression modelling demonstrated a significant negative association between birth weight z-scores and leptin for both groups. Conclusion. Maternal first trimester serum leptin demonstrates a significant negative association with neonatal weight in preeclamptic pregnancies and to a lesser extent in normotensive pregnancies. A possible leptins involvement in pathophysiological adaptations that define the foetal growth potential can be supported.