Enrico Periti

First trimester screening for Down's syndrome using maternal serum PAPP-A and free β-hCG in combination with fetal nuchal translucency thickness

The aim of this study was to evaluate the potential effectiveness of maternal serum pregnancy‐associated plasma protein A (PAPP‐A) and free β‐hCG in combination with nuchal translucency thickness in first trimester screening for Downs syndrome. Maternal serum levels of PAPP‐A and free β‐hCG were assayed in stored sera from 32 Downs syndrome and 200 unaffected pregnancies. Fetal nuchal translucency was measured by ultrasound at the time of blood sampling. Screening of Downs syndrome using a combination of maternal age, PAPP‐A, free β‐hCG and nuchal translucency would achieve a detection rate of 75.8% for a false positive rate of 5%.

Cross‐sectional and longitudinal evaluation of uterine artery Doppler velocimetry for the prediction of pre‐eclampsia in normotensive women with specific risk factors

To evaluate the performance, in the prediction of pre‐eclampsia, of (1) an abnormal mean uterine artery resistance index (RI; cross‐sectional index) at 24 weeks of gestation, (2) the individual longitudinal flow pattern of results observed at 16, 20 and 24 weeks of gestation and (3) a multiple logistic regression model including the individual longitudinal flow pattern and the mean RI at 24 weeks.

Chorion villosum does not express progesterone and estrogen receptors during the first trimester of pregnancy.

First-trimester chorion villosum plays the key role in the development of human placenta and secretes a large number of hormones and hormone-related substances. To test whether progesterone and estrogen could have regulatory effects on first-trimester chorion villosum functions, we investigated the presence of progesterone receptor (PR) and estrogen receptor (ER) in 47 chorion villosum samples from patients who underwent abortion during the first trimester of pregnancy. The study was carried out using immunohistochemical methods. No ER and PR positivity was evidenced in the 47 chorion villosum samples examined. The possibility that progesterone and estrogen play a role in the regulation of chorion villosum functions should therefore be excluded.

Development of customized fetal growth charts in twins

BACKGROUND: Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. OBJECTIVE: The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. STUDY DESIGN: Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Società Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. RESULTS: The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2–8) observations per pregnancy in dichorionic and 6 in (range, 2–11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. CONCLUSION: Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for gestation constructed in this study may provide a useful tool for a more accurate assessment of fetal growth in twin pregnancies.

Maternal serum CA 125 levels in first trimester abortion

OBJECTIVE To assess the source of maternal serum CA 125 during the first trimester of pregnancy. STUDY DESIGN CA 125 was measured in stored samples from nonviable pregnancies of 8-13 weeks gestation. The study group comprised 19 women with vaginal bleeding and 13 non-bleeders. Only patients in whom chromosome analysis of the products of conception demonstrated a normal caryotype were included. CA 125 levels were expressed in multiples of the median (MoM) for normal pregnancies of the same gestational age. RESULTS Median MoM values of CA 125 were significantly higher in women with vaginal bleeding (1.81 MoM) as compared both to non-bleeders (0.82 MoM; p < 0.01-Mann-Whitney U-test) and to the normal pregnancies (1.01 MoM; p < 0.05). No significant difference was found between non-bleeding women and controls. CONCLUSIONS The present study indicates that in non-viable pregnancies with euploid fetuses an increase in maternal serum CA 125 levels was found only in presence of decidual disruption associated to vaginal bleeding. These findings are compatible with a prevalent decidual source of this antigen.

Decidual Progesterone and Estrogen Receptors in the First Trimester of Pregnancy

Receptor content of human decidua in early pregnancy (weeks 6-12) was investigated. Fifty-three tissue samples were obtained from voluntary patients undergoing abortion and whose gestational age range from 6 to 12 weeks. Blood samples were drawn at the time of operation in order to measure circulating estradiol (E) and progesterone (P) concentrations. Tissue samples underwent first histological confirmation and then were analyzed for receptor content by immunohistochemistry (IH) and by the conventional ligand binding technique (LBA). Estrogen receptors (ER) appeared to be always undetectable by IH (53 samples). LBA measured a significant amount of ER (> 10 fmol/mg) in two samples, borderline values (3-10 fmol/mg) in 6 and no binding in the other three. No relation was apparent between PR levels and either gestational age or blood P concentration. ER were possibly downregulated by the high E levels, and their synthesis inhibited by the high P levels.

Validation of a method for noninvasive prenatal testing for fetal aneuploidies risk and considerations for its introduction in the Public Health System.

Abstract Objective: The aim of this study was to validate noninvasive prenatal testing (NIPT) for fetal aneuploidies by whole-genome massively parallel sequencing (MPS). Methods: MPS was performed on cell-free DNA (cfDNA) isolated from maternal plasma in two groups: a first set of 186 euploid samples and a second set of 195 samples enriched of aneuploid cases (n = 69); digital PCR for fetal fraction (FF) assessment was performed on 178/381 samples. Cases with <10 × 106 reads (n = 54) were excluded for downstream data analysis. Follow-up data (invasive testing results or neonatal information) were available for all samples. Performances in terms of specificity/sensitivity and Z-score distributions were evaluated. Results: All positive samples for trisomy 21 (T21) (n = 43), trisomy 18 (T18) (n = 6) and trisomy 13 (T13) (n = 7) were correctly identified (sensitivity: 99.9%); 5 false positive results were reported: 3 for T21 (specificity = 98.9%) and 2 for T13 (specificity = 99.4%). Besides FF, total cfDNA concentration seems another important parameter for MPS, since it influences the number of reads. Conclusions: The overall test accuracy allowed us introducing NIPT for T21, T18 and T13 as a clinical service for pregnant women after 10 + 4 weeks of gestation. Sex chromosome aneuploidy assessment needs further validation due to the limited number of aneuploid cases in this study.

Cell‐free DNA testing in the maternal blood in high‐risk pregnancies after first trimester combined screening

The objective of this study was to investigate a strategy for clinical implementation of cell‐free DNA (cfDNA) testing in high‐risk pregnancies after first‐trimester combined screening.

First trimester contingent screening for trisomies 21,18,13: is this model cost efficient and feasible in public health system?

Abstract Purpose: To evaluate the effectiveness of three different first trimester screening models for trisomies 21, 18 and 13, in terms of detection rate, invasive test rate and final costs. Material and methods: We analyzed the distribution of risk for trisomies 21, 18 and 13 in a population of 20,831 singleton pregnancies based on maternal age, fetal heart rate, nuchal translucency, free beta human chorionic gonadotropin and pregnancy-associated plasma protein A (Combined test). On the basis of our data, we estimated the performance and cost of screening for trisomies using three different models at specific cutoffs: Combined test; Cell free DNA test and Contingent screening test. Results: Using Combined test, DR for major trisomies was estimated to be 94.92%, invasive test rate was 6.3%. cfDNA would result in a DR of 97.92%, with an invasive test rate of 3.64%. Contingent screening approach would result in an overall DR of 97.82, with a rate for invasive procedure of 1.36% and a final cost lower than other screening policies (2,338,433 euro vs 5,796,060 of cfDNA and 2,385,473 of Combined test). Conclusions: Contingent screening test could be a cost-efficient and feasible first trimester screening test for aneuploidies in public health system.

P069: The genetic sonogram: experience with isolated ultrasound soft markers in 1463 high-risk pregnancies

artery was determined. Data are reported as mean ± 1 SD and analysed by paired t test. Results: No statistically significant behavioural-state-related changes were observed for UV time-average velocity and UV volume flow, resulting in UV volume flow per kg fetus of 69.1 ± 14.9 ml/min/kg at 1F and 71.6 ± 12.1 ml/min/kg at 2F (ns). A statistically significant increase (p = 0.02) was established for UV cross-sectional area (46.4 ± 8.6 mm2 vs 49.0 ± 10.1 mm2) and for FHR from 134.2 ± 10.3 bpm in 1F to 144.2 ± 7 bpm in 2F. Umbilical artery PI was not significantly different between the two behavioural states. Conclusion: It can be concluded that on the basis of high venous vessel wall compliance, the significant increase in UV cross-sectional area during fetal behavioural state 2F may be determined by a rise in mean venous pressure. The significant rise in FHR may reflect elevated fetal cardiac output during this behavioural state. This is further supported in part by a mild increase in UV volume flow.