Dimitra Kappou

Maternal serum insulin-like growth factor-I at 11-13 weeks in preeclampsia.

To investigate the maternal serum concentration of insulin‐like growth factor‐I (IGF‐I) in the first trimester of pregnancies that subsequently develop preeclampsia (PE) and to examine the possible association with uterine artery pulsatility index (PI).

Recent advances in optical imaging for cervical cancer detection

Cervical cancer is one of the most common and lethal gynecological malignancies in both developing and developed countries, and therefore, there is a considerable interest in early diagnosis and treatment of precancerous lesions. Although the current standard care mainly based on cytology and colposcopy has reduced rates of cervical cancer morbidity and mortality, many lesions are still missed or overcalled and referred for unnecessary biopsies. Optical imaging technologies, spectroscopy approaches and high-resolution imaging methods are anticipated to improve the conventional cervical cancer screening providing in vivo diagnosis with high sensitivity and specificity. Their concept is that morphologic and biochemical properties of the cervical tissue are altered in response to its malignant transformation. In addition, contrast agents that target against specific neoplastic biomarkers can enhance the effectiveness of this new technology. Due to the unprecedented growth of these optical techniques accompanied probably by favorable cost-effectiveness, the primary detection of premalignant lesions may become more accessible in both the developing and the developed countries and can offer see-to-treat workflows and early therapeutic interventions.

Maternal serum insulin-like growth factor-binding protein-3 (IGFBP-3) at 11-13 weeks in preeclampsia.

The objective of this study was to determine if the maternal serum concentration of insulin-like growth factor-binding protein-3 (IGFBP-3) at 11–13 weeks gestation is altered in pregnancies that subsequently develop preeclampsia (PE). Maternal serum concentration of IGFBP-3, pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (PI) were measured in 60 cases that developed PE, including 20 that developed early-PE requiring delivery before 34 weeks, and compared with 120 unaffected controls. In the unaffected pregnancies, the median multiple of the normal median (MoM) values of serum IGFBP-3, PAPP-A and uterine artery PI were 1.0 MoM. In late-PE, but not in early-PE, serum IGFBP-3 was significantly increased (1.16 and 1.06 MoM, respectively), whereas in early-PE, but not in late-PE, uterine artery PI was increased (1.41 and 1.11 MoM, respectively) and serum PAPP-A was decreased (0.53 and 0.87 MoM, respectively). In the PE group, there was no significant association between IGFBP-3 and either uterine artery PI (P=0.775) or maternal serum PAPP-A (P=0.275). First-trimester serum IGFBP-3 is increased in pregnancies that subsequently develop late-PE in a mechanism that is unrelated to impaired placentation, as reflected in uterine artery PI and serum PAPP-A.

Maternal serum placental growth hormone at 11–13 weeks’ gestation in pregnancies delivering small for gestational age neonates

Objective: To investigate whether the maternal serum concentration of human placental growth hormone (PGH) at 11–13 weeks’ gestation is altered in pregnancies that deliver small for gestational age (SGA) neonates. Methods: Maternal serum concentration of PGH was measured in 60 cases that subsequently delivered SGA neonates in the absence of preeclampsia and compared to 120 non-SGA controls. Results: In the SGA group, compared to the non-SGA group, there was no significant difference in the median PGH MoM (0.95 MoM, IQR 0.60–1.30 vs. 1.00 MoM, IQR 0.70–1.30, p = 0.97). There was no significant association between PGH MoM and birth weight percentile in either the SGA (p = 0.72) or in the non-SGA group (p = 0.63). Conclusion: Maternal serum PGH at 11–13 weeks’ gestation is unlikely to be a useful biochemical marker for early prediction of SGA.

Maternal Serum Human Placental Growth Hormone (hPGH) at 11 to 13 Weeks of Gestation in Preeclampsia

Objective. Human placental growth hormone (hPGH) is produced by human placenta and plays a central role in the maternal metabolic adjustments to pregnancy. The objective of this study was to investigate the maternal serum concentration of hPGH at 11–13 weeks of gestation in pregnancies that subsequently developed preeclampsia (PE), and to examine the possible association with uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A). Methods. The maternal serum concentration of hPGH at 11–13 weeks was measured in a case–control study from 60 cases that developed PE and 120 unaffected controls. The measured hPGH concentration was converted into a multiple of the expected median (MoM) in unaffected pregnancies. Regression analysis was used to determine the significance of association between hPGH MoM with uterine artery PI MoM and PAPP-A MoM. Results. In the pregnancies that subsequently developed PE the median serum hPGH concentration was not significantly different from that in the unaffected group (0.92 versus 1.00 MoM), whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no significant association between serum hPGH MoM and gestational age at delivery, uterine artery PI MoM, or serum PAPP-A MoM. Conclusion. The finding that in the PE group serum hPGH level during the first trimester is normal suggests that it is unlikely that this hormone plays a role in the pathogenesis of PE.

Noninvasive prenatal diagnosis of Down syndrome: current knowledge and novel insights.

Abstract The noninvasive prenatal diagnosis of trisomy 21 (Down syndrome) is an actively researched area of prenatal medicine, as this is the most common aneuploidy compatible with life and a major cause of mental retardation. The isolation of intact fetal cells, and most importantly, the successful detection of fetal-origin nucleic acids (cell-free fetal DNA and RNA), in maternal plasma even from the early stages of pregnancy has inspired scientists to develop discriminative genetic markers for the prenatal detection of aneuploidy. In the near future, the development of epigenetic fetal-specific markers will possibly allow the universal application of a cell-free fetal DNA-based diagnostic test regardless of the gender of the fetus or its polymorphic status. Other promising approaches rely upon the detection of free placentally derived RNA transcribed from genes located on chromosome 21 and the application of highly sensitive techniques, such as digital polymerase chain reaction and high-throughput shotgun sequencing. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of fetal origin nucleic acids poses severe technical challenges. In this review article, we present an overview of the current knowledge in the field of noninvasive prenatal assessment of fetuses with Down syndrome and the future perspectives regarding new fetal markers and novel molecular techniques that may eventually be applied in the clinical setting as a valid and safe option for women who opt for noninvasive accurate prenatal diagnosis.

Cervical length at 11–40 weeks: unconditional and conditional longitudinal reference ranges

Our aim was to establish unconditional and conditional longitudinal reference ranges for cervical length throughout pregnancy.

Fetal volume at 11-14 gestational weeks: reference ranges and association with first trimester biochemical and biophysical markers.

Abstract Aims: To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11–14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters. Methods: Prospective observational study on 240 fetuses at 11–14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided Analysis. Pearson correlation coefficient (cc) and regression analysis were used. Results: FV increased exponentially with crown rump length and was unrelated to maternal weight (cc=–0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76), smoking status (t-test, P=0.149) and mode of conception (t-test, P=0.8). Z-scores (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=–0.026, P=0.733), log10 multiples of the median (MoM) free beta human chorionic gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was significantly positively correlated with log10 MoM pregnancy associated plasma protein-A (PAPP-A; regression coefficient=1.420976, R2=0.0957, P<0.0001). Conclusions: FV is strongly related to PAPP-A even after adjustment for crown rump length with a mechanism unrelated to placental perfusion. FV is independent of the vast majority of first trimester parameters; hence, it is a promising marker of early fetal growth.

Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative genomic hybridization array: molecular cytogenetic analysis, fetal pathology and review of the literature

BACKGROUND Partial trisomy of the long arm of chromosome 1 (1q) is an exceptionally rare chromosomal abnormality and most of the prenatally diagnosed cases are associated with either complete (q11-qter) or large (q21-qter) duplications with pre- or perinatal demise of all reported cases. The most common sonographic findings associated with this karyotype abnormality include ventriculomegaly, increased nuchal translucency or nuchal fold, renal and cardiac abnormalities, craniofacial dysmorphism, and limb deformities. However, there is a wide spectrum of clinical manifestations due to the great variability in the extent of the duplication size and the possible contribution of additional genetic rearrangements in the final phenotype. CASE REPORT We report on a female fetus with sole partial trisomy 1q presenting with multiple structural malformations in the second trimester scan. Standard karyotyping demonstrated a large duplication on the proximal end of chromosome 1 [46,XX,dup(1)(pter→q31::q31→q12::q31→qter)] and further application of comparative genomic hybridization array confirmed the diagnosis and offered a precise characterization of the genetic defect. CONCLUSION A fetus with nonmosaic partial trisomy 1q that was prenatally diagnosed upon multiple abnormal ultrasound findings is presented. A detailed review of the currently available literature on the prenatal diagnostic approach of partial trisomy 1q in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided. The use of novel molecular techniques such comparative genomic hybridization array could shed further light on the correlation between the genes identified in the chromosomal region of interest and the resultant phenotype.

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks in trisomy 21 and trisomy 18 pregnancies.

OBJECTIVE To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 in first-trimester screening for fetal aneuploidies. STUDY DESIGN Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation were measured and compared in 30 trisomy 21, 30 trisomy 18 and 120 euploid pregnancies. RESULTS The median multiple of the normal median (MoM) values of maternal serum IGF-I, IGFBP-1 and IGFBP-3 in trisomy 21, trisomy 18 and euploid pregnancies were not significantly different (IGF-I: 1.10, 1.14 and 1.0 MoM, respectively; IGFBP-1: 1.10, 1.01 and 1.0 MoM; IGFBP-3: 0.90, 1.16 and 0.98 MoM). CONCLUSION Measurement of maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation is unlikely to be useful in screening for trisomies 21 and 18.