TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

White matter changes in fetal brains with ventriculomegaly.

Introduction: Ventriculomegaly (VM) is a fetal brain malformation which may present independently (isolated form) or in association with different cerebral malformations, genetic syndromes or other pathologies (non-isolated form). Methods: This paper aims to study the effect of ventriculomegaly on the internal tridimensional architecture of fetal brains by way of Klingler's dissection. Ventriculomegaly was diagnosed using fetal ultrasonography during pregnancy and subsequently confirmed by necropsy. Taking into consideration the diameter of the lateral ventricle (measured at the level of the atrium), the brains were divided into two groups: moderate ventriculomegaly (with atrial diameter between 13 and 15 mm) and severe ventriculomegaly (with atrial diameter above 15 mm). Results and discussion: The results of each dissection were described and illustrated, then compared with age-matched reference brains. In the pathological brains, fascicles in direct contact with the enlarged ventricles were found to be thinner and displaced inferiorly, the opening of the uncinate fasciculus was wider, the fornix was no longer in contact with the corpus callosum and the convexity of the corpus callosum was inverted. We have studied the prevalence of neurodevelopmental delay in children born with ventriculomegaly in the literature and discovered that a normal developmental outcome was found in over 90% of the mild VM cases, approximately 75% of the moderate and 60% in severe VM, with the correlated neurological impairments ranging from attention deficits to psychiatric disorders.

Ultrasound Placental Remodeling Patterns and Pathology Characteristics in Patients with History of Mild SARS-CoV-2 Infection during Pregnancy.

Introduction: This research aims to describe a progressive pattern of ultrasound placental remodeling in patients with a history of SARS-CoV-2 infection during pregnancy. Materials and Methods: This was a longitudinal, cohort study which enrolled 23 pregnant women with a history of former mild SARS-CoV-2 infection during the current pregnancy. Four obstetricians analyzed placental ultrasound images from different gestational ages following COVID infection and identified the presence and degree of remodeling. We assessed the inter-rater agreement and the interclass correlation coefficients. Pathology workup included placental biometry, macroscopic and microscopic examination. Results: Serial ultrasound evaluation of the placental morphology revealed a progressive pattern of placental remodeling starting from 30-32 weeks of gestation towards term, occurring approximately 8-10 weeks after the SARS-CoV-2 infection. Placental changes-the "starry sky" appearance and the "white line" along the basal plate-were identified in all cases. Most placentas presented normal subchorionic perivillous fibrin depositions and focal stem villi perivillous fibrin deposits. Focal calcifications were described in only 13% of the cases. Conclusions: We identified two ultrasound signs of placental remodeling as potential markers of placental viral shedding following mild SARS-CoV-2. The most likely pathology correspondence for the imaging aspect is perivillous and, respectively, massive subchorionic fibrin deposits identified in most cases.

Umbilical Cord Biometry and Fetal Abdominal Skinfold Assessment as Potential Biomarkers for Fetal Macrosomia in a Gestational Diabetes Romanian Cohort.

Backgroundand Objectives: Gestational diabetes mellitus (GDM) is a pregnancy-associated pathology commonly resulting in macrosomic fetuses, a known culprit of obstetric complications. We aimed to evaluate the potential of umbilical cord biometry and fetal abdominal skinfold assessment as screening tools for fetal macrosomia in gestational diabetes mellitus pregnant women. Materials and methods: This was a prospective case−control study conducted on pregnant patients presenting at 24−28 weeks of gestation in a tertiary-level maternity hospital in Northern Romania. Fetal biometry, fetal weight estimation, umbilical cord area and circumference, areas of the umbilical vein and arteries, Wharton jelly (WJ) area and abdominal fold thickness measurements were performed. Results: A total of 51 patients were enrolled in the study, 26 patients in the GDM group and 25 patients in the non-GDM group. There was no evidence in favor of umbilical cord area and WJ amount assessments as predictors of fetal macrosomia (p > 0.05). However, there was a statistically significant difference in the abdominal skinfold measurement during the second trimester between macrosomic and normal-weight newborns in the GDM patient group (p = 0.016). The second-trimester abdominal circumference was statistically significantly correlated with fetal macrosomia at term in the GDM patient group with a p value of 0.003, as well as when considering the global prevalence of macrosomia in the studied populations, 0.001, when considering both populations. Conclusions: The measurements of cord and WJ could not be established as predictors of fetal macrosomia in our study populations, nor differentiate between pregnancies with and without GDM. Abdominal skinfold measurement and abdominal circumference measured during the second trimester may be important markers of fetal metabolic status in pregnancies complicated by GDM.

The Evaluation of the Four-Chamber Cardiac Dissection Method of the Fetal Heart as an Alternative to Conventional Inflow-Outflow Dissection in Small Gestational-Age Fetuses.

The examination of very small fetal hearts requires special equipment and a specialist that are not available in many general pathology laboratories. Compared to conventional examination, the four-chamber cardiac dissection (4CCD) method can be performed by any pathologist using instruments generally available in pathology services. The aim of this study is to evaluate the efficiency of the 4CCD method in the examination of small fetal hearts using post-mortem magnetic resonance imaging (pm-MRI) at 7T as the standard. Twelve fetuses with gestational ages between 13 and 19 weeks have been included in this study. All fetuses underwent pm-MRI examination prior to pathologic examination. The 4CCD method was used for the cardiac examination in all cases following the same guidelines for cardiac sectioning. The 4CCD was able to identify all cardiac anatomic structures as compared to pm-MRI at 7T, demonstrating a sensibility of 95.8% (95% CI, 94.5-95.8) and specificity of 100% (95% CI, 32.3-100). The overall accuracy in identifying cardiac anatomic structures was 95.8% (95% CI, 93.4-95.8). Additionally, the 4CCD method was able to detect cardiac anomalies with an overall diagnostic accuracy of 91% (95% CI, 85.8-94.2), sensibility of 67.6% (95% CI, 54.5-75.3), and specificity of 97% (95% CI, 93.7-99) as compared to pm-MRI at 7T. The four-chamber view dissection method can be considered as an alternative to the conventional inflow-outflow dissection method in selected cases.

Diagnostic value of virtual autopsy using pm-MRI at 3T on malformed second trimester fetuses vs classic autopsy.

OBJECTIVE: To determine the diagnostic value of virtual autopsy using post mortem-MRI (pm-MRI) at 3Tesla (T) compared to classic autopsy for the confirmation of fetal structural anomalies and secondly to establish which cases of termination of pregnancy would benefit mostly from a virtual autopsy. METHODS: In each of 32 fetuses included in the study, 32 anatomical structures were assessed, after termination of pregnancy in the second trimester. All cases were evaluated by prenatal ultrasonography, virtual autopsy and classic autopsy, and then divided into four groups: Cerebral Group, Cardiac Group, Renal Group and Other Group (miscellaneous group). The concordance of virtual autopsy with classic autopsy was calculated overall and for each group and each structural item. Also, the concordance between the two methods was assessed using a diagnostic error score (DgE_score), calculated as the absolute value of the difference between the number of malformations detected by classic autopsy per case (CA score) and the number of malformations detected at virtual autopsy per case (VA score). RESULTS: Overall virtual autopsy demonstrated a diagnostic sensitivity (Se) compared to classic autopsy of 67.33% [95% CI 57.28-76.33], with a specificity (Sp) of 98.37% [95% CI 97.33-99.09], a positive predictive value (PPV) of 81.93% [95% CI 71.95-89.52], a negative predictive value (NPV) of 96.49% [95% CI 95.11-97.57] achieving a diagnostic accuracy of 95.31% [95% CI 93.83-96.52]. Overall, no statistic significant correlation was demonstrated between DgE_score and the gestational age of the fetuses or between DgE_score and the weight of the fetuses, but a significant correlation was revealed between the virtual autopsy and classic autopsy score. The diagnostic utility of virtual autopsy using pm-MRI at 3 T as compared to classic autopsy for each category of termination of pregnancy revealed in the Cerebral Group a Se of 80.00% [95% CI 28.36-99.49], with a 96.30% [95% CI 81.03-99.91], a PPV of 80.00% [95% CI 35.75-96.64] a NPV of 96.30% [95% CI 81.81-99.34], with a diagnostic accuracy of 93.75% [95% CI 79.19% to 99.23] and a Cohen's Kappa coefficient of 0.76 [95% CI 0.4494-1.0765]; in the Renal Group a Se and Sp of 100%, but in the Cardiac Group the Se was only 60.00% [95% CI 26.24-87.84], Sp 75% [95% CI 34.91-96.81], the PPV 75.00% [95% CI 44.92-91.69], NPV 60% [95% CI 38.87-77.96], with a diagnostic accuracy of 66.67% [95% CI 40.99-86.66] and a Cohen's Kappa coefficient of 0.32 [95% CI -0.07-0.76]. CONCLUSIONS: The results support virtual autopsy using pm-MRI at 3T as a reliable alternative to classic autopsy for the non-forensic analysis of second trimester fetuses. Analyzing the diagnostic utility of virtual autopsy using pm-MRI at 3 T for the confirmation of prenatal ultrasound findings in second trimester fetuses as compared to classic autopsy, the best results were obtained in the Cerebral and Renal Group. Reserved results were found in the Cardiac Group. Therefore, for the pregnancies with termination of pregnancy for cerebral or renal abnormalities, virtual autopsy by pm-MRI at 3T can be taken into consideration as a first-line investigation to confirm the prenatal findings.

White Matter Dissection of the Fetal Brain.

Neuroplasticity is a complex process of structural and functional reorganization of brain tissue. In the fetal period, neuroplasticity plays an important role in the emergence and development of white matter tracts. Here, we aimed to study the architecture of normal fetal brains by way of Klingler's dissection. Ten normal brains were collected from in utero deceased fetuses aged between 13 and 35 gestational weeks (GW). During this period, we observed modifications in volume, shape, and sulci configuration. Our findings indicate that the major white matter tracts follow four waves of development. The first wave (13 GW) involves the corpus callosum, the fornix, the anterior commissure, and the uncinate fasciculus. In the second one (14 GW), the superior and inferior longitudinal fasciculi and the cingulum could be identified. The third wave (17 GW) concerns the internal capsule and in the fourth wave (20 GW) all the major tracts, including the inferior-occipital fasciculus, were depicted. Our results suggest an earlier development of the white matter tracts than estimated by DTI tractography studies. Correlating anatomical dissection with tractography data is of great interest for further research in the field of fetal brain mapping.

Association between maternal/newborn genetic variants, placental pathology and spontaneous preterm birth risk: a Romanian population-based study.

Objective: The objective of this study was to determine the association between maternal/newborn single-nucleotide polymorphisms (SNPs) in three candidate genes, placental pathology and the risk of spontaneous preterm birth (SPTB) in a Romanian population.Methods: We performed a prospective case-control study in a tertiary maternity in Romania, including 79 mother-newborn pairs with SPTB and 81 mother-newborn pairs with term delivery. Using real-time Polymerase Chain Reaction (PCR), three SNPs rs8192282 A > G, rs2277698 C > T and rs34003 A > C located on interleukin 6 receptor (IL6R), tissue inhibitor of matrix metalloproteinase-2 (TIMP2) and fibroblast growth factor 1 (FGF1) genes were assessed. The minor allele and genotype frequencies were compared between groups. Multilocus genetic association analyses were performed. From pathology reports, the morphological and histopathological examination of the placentas were extracted.Results: The rs34003 C/C genotype frequency in newborns FGF1 gene was significantly higher in the spontaneous preterm birth (SPTB) group compared to the control group (p = .045). In single-locus analyses, C/C genotype was associated with an increased risk of spontaneous preterm birth (OR = 2.59, 95%CI: 1.02-6.58). Additionally, this homozygote genotype was correlated with the presence of placental pathology, especially with the inflammatory and vascular lesions (p < .01). The prediction model based on rs34003 C/C genotype - placental pathology joint influence had a statistically significant regression coefficient (p < .01, OR = 7.76, 95%CI: 4.03-14.93). Single nucleotide polymorphisms related to IL6R gene in maternal samples and FGF1 gene in newborns were associated with spontaneous preterm delivery in multilocus genetic association analyses (p = .028, OR of 2.375).Conclusions: Our results indicate that rs34003 C/C genotype in newborns FGF1gene is correlated with the occurrence of placental pathological lesions and with an increased SPTB risk. The association of two SNPs in maternal and fetal genes doubled the risk of spontaneous preterm birth in our population.

Renin-angiotensin system gene variants and risk of early- and late-onset preeclampsia: A single center case-control study.

BACKGROUND: Changes in the renin-angiotensin-aldosterone system's (RAAS) activity due to different genetic variations could represent risk factors for the onset of preeclampsia. OBJECTIVE: To test and quantify the relationships of 8 RAAS gene polymorphisms (angiotensinogen (AGT)-M235T, AGT-T174M, angiotensin converting enzyme (ACE)-I/D, ACE8-A2350G, angiotensin II type 1 receptor (AGTR1)-A1166C, angiotensin II type 2 receptor (AGTR2)-C3123A, renin (REN)-G83A, aldosterone synthase (CYP11B2)-T344C) with susceptibility to early- (EOPE) and late-onset preeclampsia (LOPE). STUDY DESIGN: We performed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis in 217 pregnant women, of whom 87 pregnant women with EOPE/LOPE and 130 normal pregnant women. The relationship between the studied RASS gene polymorphisms and EOPE/LOPE was tested by multiple logistic regressions. RESULTS: The multivariate logistic regression analysis showed that AGT-M235T (adjusted OR = 4.63), AGT-T174M (adjusted OR = 4.13), REN-G83A (adjusted OR = 3) and CYP11B2-C344T (adjusted OR = 3.13) gene polymorphisms remained independent risk factors for EOPE. Moreover, ACE-I/D (adjusted OR = 4.04), ACE-A2350G (adjusted OR = 3.5), AGTR1-A1166C (adjusted OR = 2.73), and REN-G83A (adjusted OR = 2.67) polymorphisms remained independent risk factors for LOPE. The frequency of overweight was significantly different (p = 0.001) in pregnant women with EOPE, LOPE and the control group (LOPE:16, 29.6% vs. EOPE:12, 36.4% vs. control group:16, 12.3%). Pregnant women with EOPE had babies with a significantly lower mean birth weight (2067.9 ±â€¯887.9) in comparison to women with LOPE (mean ±â€¯SD: 2860.1 ±â€¯771.1, p < 0.001) and women with normal pregnancies, respectively (mean ±â€¯SD: 3324.9 ±â€¯484.9, p < 0.001). CONCLUSION: We confirmed the influence of the renin-angiotensin-aldosterone system through these 8 genetic variations on the onset of preeclampsia.

The influence of reproductive factors on breast cancer risk in women with pathogenic mutations.

PURPOSE: To assess the influence of reproductive factors in the occurrence of breast cancer in women, taking into account the presence/absence of genetic predisposing mutations. METHODS: 100 patients with breast cancer were included. The genetic testing was conducted through a multigene panel. Reproductive characteristics were noted for all patients: age of menarche, age of the patient at first full term pregnancy, number of pregnancies, number of full-term pregnancies, breastfeeding interval, number of abortions, and menopausal status at the time of diagnosis. The patients were divided into three groups according to their mutations: BRCA1, positive for mutations other than BRCA1 and negative. RESULTS: The risk of breast cancer was not influenced by the number of abortions, parity, age at first pregnancy, age at menarche and menopausal status, or by oral contraceptive use in carriers of pathogenic mutations group in the BRCA1 group. The present study has demonstrated the protective effect of breastfeeding only in patients without genetic risk (p=0.0344). In contrast, breastfeeding did not influence breast cancer occurrence in BRCA1 mutation carriers' group (p=0.2321). CONCLUSIONS: Breastfeeding represents a protective mechanism only in patients without genetic breast cancer predisposing mutations. Environmental and reproductive factors can impact the risk and the age of onset of breast cancer in patients carrying pathogenic mutations, but the mechanisms of action are not fully understood.

Birth defects in Tarnaveni area, Romania - preliminary study results.

BACKGROUND AND AIMS: In the development of any human body, defects may occur, resulting in the occurrence of congenital malformations, also referred to as birth defects. The aim of this preliminary study was to assess the prevalence of birth defects registered during a period of 5 years in Tarnaveni area. As Tarnaveni is located in close proximity to a former chemical plant, a recognized hazardous waste site, we conducted this pilot study to assess the prevalence of birth defects, in order to evaluate the need for a more comprehensive investigation of a potential relation between the exposure to toxic metals contaminating the environmental media as a result of the past industrial activities, and the prevalence of the birth defects in this area. METHODS: We abstracted birth information (gestational age at delivery (GA), birth weight (BW), birth length (BL), head circumference (HC), and major structural birth defects), from medical records at "Dr. Gheorghe Marinescu" Tarnaveni Municipal Hospital, of the 2010-2014 period. We expressed BW as Z-scores relative to expected mean values at each gestational age for a reference population, calculated the ponderal index, and determined the 5 years birth defects prevalence among live births during the study interval. RESULTS: The 5 years (2010-2014) prevalence of birth defects, was 3.3% (95% confidence interval (CI): 2.47, 4.09). There were n = 163 (8.7%) preterm deliveries (less than 37 weeks of gestation at delivery), mean birth weight was 3108.3 g (standard deviation (SD) = 517.1), ranging from 450-4600 g, and n = 187 (10%) were low birth weight (LBW) (less than 2500 g). The ponderal index was 2.2 g/cm3 on average (SD = 0.5), with range 1.2-20.7 g/cm3. CONCLUSIONS: While preliminary, our data show a 5 years (2010-2014) prevalence of major structural birth defects among newborns from Tarnaveni area of 3.3%. These pilot results indicate the need for a more comprehensive investigation of a potential relation between the exposure to toxic metals contaminating the environmental media as a result of the past industrial activities and the prevalence of the birth defects in Tarnaveni area.

Potential clinical benefits and limitations of fetal virtopsy using high-field MRI at 7 Tesla versus stereomicroscopic autopsy to assess first trimester fetuses.

OBJECTIVE: The aim of this study was to establish the diagnostic accuracy of high-field magnetic resonance imaging (MRI) at 7 Tesla (T) compared with that of stereomicroscopic autopsy for assessing first trimester fetuses. METHODS: Nine consecutive cases of first trimester fetuses resulting from spontaneous and therapeutic pregnancy termination were considered. The cases were divided into two groups according to gestational age: the Embryo Group with cases of nine to 10 gestational weeks (GWs) and the Fetus Group with cases of 13 GWs. The first group was scanned using three-dimensional fast imaging with steady state precession (3D FISP), and the second group was scanned using a two-dimensional (2D) turbo spin-echo high-resolution T2-weighted imaging (T2 WI) protocol. A radiologist and two embryologists interpreted the images. All cases were evaluated by invasive autopsy, with pathologist blinded to the imaging results. In total, the database included 270 items for evaluation (9 cases × 30 structures/case). RESULTS: The global agreement between fetal high-field virtopsy and microscopic or stereomicroscopic autopsy was evaluated using 225 evaluation items visible by both methods. Overall, using microscopic examination and stereomicroscopic autopsy as the gold standard, fetal high-field virtopsy had a sensitivity of 94.6% [95% CI, 87.2-98.3] and a specificity of 97.6% [95% CI, 95-98.8]. The positive predictive value (PPV) was 93% [95% CI, 85.7-96.6], and the negative predictive value (NPV) was 98.2% [95% CI, 95.7-99.4]. Cohen kappa coefficient of agreement was k = 0.92 [95% CI, 0.82-0.97], and the McNemar test showed p = 1.00. CONCLUSIONS: Virtual autopsy using high-field MRI at 7 T can be considered a safe alternative approach to stereomicroscopic autopsy for the assessment of fetal structural anomalies at the end of the first trimester of pregnancy.

Assessment of heavy metals (total chromium, lead, and manganese) contamination of residential soil and homegrown vegetables near a former chemical manufacturing facility in Tarnaveni, Romania.

Our aim was to assess local population exposure to heavy metals resulting from soil and vegetable contamination in Tarnaveni, Romania, an area located near a former chemical factory. We collected residential soil and vegetable samples from Tarnaveni and measured chromium (Cr), lead (Pb), and manganese (Mn) levels by atomic absorption spectrometry. We evaluated the relationship between soil and vegetable metals and the distance from the shuttered chemical factory, and calculated the hazard index to assess local population metal exposure via contaminated vegetable ingestion. Soil metal concentrations ranged between 15.6 and 525.8 mg/kg for total Cr, between 25.4 and 559.5 mg/kg for Pb, and between 363.1 and 1389.6 mg/kg for Mn. We found average concentrations of 17.8 mg/kg for total Cr, 2.2 mg/kg for Pb, and 116.6 mg/kg for Mn in local vegetables. We found soil concentrations for all three metals that exceeded normal background levels according to Romanian regulations (Pb exceeded 100 mg/kg in some of the samples), as well as measurable concentrations of metals in all analyzed vegetable samples. These preliminary data underscore a need for a more extensive investigation into associated adverse health effects in the exposed population.

Prevalence of deleterious mutations among patients with breast cancer referred for multigene panel testing in a Romanian population.

AIM: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing is becoming more common in medical care.We report our experience regarding deleterious mutations of high and moderate-risk breast cancer genes (BRCA1/2, TP53, STK11, CDH1, PTEN, PALB2, CHEK2, ATM), as well as more recently identified cancer genes, many of which have increased risk but less well-defined penetrance. METHODS: Genetic testing was performed in 130 consecutive cases with breast cancer referred to our clinic for surgical evaluation and who met the 2016 National Comprehensive Cancer Network (NCCN) criteria for genetic testing. RESULTS: 82 patients had pathogenic/likely pathogenic mutations and VUS mutations, and 48 were negative; 36 of the pathogenic mutations were in the high-risk genes and 16 were in the moderate risk genes and only 5 cases in the intermediary risk group.From the VUS mutation group 21 cases were in the intermediary risk group, 9 cases were in the moderate risk group and only 7 cases in high risk group.The most frequent BRCA1 variant was c.3607C>T (7 cases) followed by c.5266dupC and c.4035delA (each in 4 cases). Regarding BRCA-2 mutations we identified c.9371A>T and c.8755-1G>A in 6 cases and we diagnosed VUS mutations in 3 cases. CONCLUSION: Our study identified 2 mutations in the BRCA1 gene that are less common in the Romanian population, c.3607C>T and c.4035delA. Both variants had particular molecular phenotypes, c.3607C>T variant respecting the triple negative pattern of BRCA1 breast cancer while c.4035delA were Luminal B HER positive.

A couples-focused intervention for smoking cessation during pregnancy: The study protocol of the Quit Together pilot randomized controlled trial.

Tobacco smoking remains the leading global cause of preventable disease and death. Preconception and pregnancy smoking are high in Central and Eastern Europe. Quit Together is a partnership between a US university and a Romanian university, obstetrics and gynecology clinics in Romania, and other community partners in Romania. The objective of the Quit Together pilot study is to adapt, enhance and test the implementation feasibility and initial efficacy of an evidence-based pregnancy and postnatal couple intervention for smoking cessation in Romania. Quit Together builds on the Motivation and Problem Solving (MAPS) approach, enhanced by targeting the couples' smoking behavior and focusing on dyadic efficacy for smoking cessation. The study is an ongoing randomized controlled trial of 120 Romanian pregnant smokers and their partners. Participants are randomized to: 1) an intervention arm consisting, typically, of up to 8 prenatal and postnatal telephone counseling calls for the women and 4 for their partners, combining motivational strategies and problem-solving/coping skills to encourage the woman to quit smoking and the partner to support her decision; and 2) a control arm (usual care). The primary outcome is maternal biochemically verified smoking abstinence at 3 months postpartum. Quit Together has the potential to identify effective strategies to increase maternal smoking cessation during pregnancy and smoking abstinence after birth. If effective, Quit Together is expected to have a sustainable positive impact on the health of the child, mother and partner, and potentially reduced health system costs.

Maternal/fetal eNOS-Glu298Asp genotypes and their influence on the severity, prognosis, and lipid profile of preeclampsia.

OBJECTIVES: To analyze the contribution of maternal eNOS-Glu298Asp genotypes and also the association with fetal genotypes to the development of preeclampsia, prognosis, and maternal dyslipidemia. METHODS: Sixty-nine pairs of preeclamptic mothers/newborns and 94 pairs of normotensive mothers/newborns were genotyped for eNOS-Glu298Asp using PCR-RFLP methods. RESULTS: Women carriers of at least one Asp298 allele had a 1.53-fold (p = NS), 1.88-fold (p = NS), and 2.08-fold (p = .05), respectively, increased risk to develop PIH, mild, or severe preeclampsia. If both the mother and the newborn were carriers of the Asp298 allele, the risk for preeclampsia was 5.09-fold higher (p < .001). Preeclamptic women with severe preeclampsia had significantly higher cholesterol (mg/dl, 287.23 ± 43.01 versus 235.36 ± 45.01, p = .02) and LDL (mg/dl, 194.9 ± 42.8 versus 144.98 ± 54.84, p = .04) levels and lower HDL levels (mg/dl, 32.12 ± 5.48 versus 57.84 ± 20.59, p = .02) compared to noncarriers. Also, higher LDL levels (mg/dl, 188.76 ± 46.61 versus 136.75 ± 41.85, p = .03) and lower HDL levels (mg/dl, 32.8 ± 5.64 versus 61.06 ± 22.45, p = .02) were found in preeclamptic women with severe preeclampsia whose newborns were carriers of the Asp298 allele. CONCLUSIONS: The eNOS-Glu298Asp variant (in mothers and newborns) in association with dyslipidemia could affect bioavailability of NO and could represent an increased risk for preeclampsia.

D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

AIM: To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. MATERIALS AND METHODS: We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. RESULTS: Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. CONCLUSION: The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

Complete atrioventricular septal defect in the era of prenatal diagnosis.

Complete atrioventricular septal defect (CAVSD) is a fetal cardiac malformation (5% of all cardiac malformations) that can be detected prenatally with a reserved prognosis. The diagnosis can be suspected early at the end of the first trimester using the transabdominal or transvaginal ultrasound approach. Generally, the diagnostic can be established during the mid-trimester scan at 19-24 weeks of gestation. The percentage of antenatal diagnostic of CAVSD is between 57-92%. This review aims to analyze the anatomical principles and the ultrasound techniques that can improve the prenatal diagnosis of CAVSD. We have also analyzed the structural and genetic anomalies frequently associated with CAVSD.

VEGF +936 C/T Genetic Polymorphism in Patients with Cervical Dysplasia.

Aim. The present study aims to analyze the potential role of VEGF +936 C/T polymorphism in cervical intraepithelial neoplasia. Material and Method. One hundred and eighty-six patients were included in the study: 75 cases (patients diagnosed with CIN) and 111 controls (negative for both HPV testing and cytology). For each patient a single visit was scheduled when colposcopy was performed. From cervical specimen, cytology and HPV testing were performed and from peripheral blood VEGF +936 genotyping was determined. For statistical analysis purposes OR and chi-square were used at a level of significance of <0.05. Results. No link has been found in the detection of CT genotype in cases versus controls, OR = 0.8295, [0.42, 1.62]. An inverse correlation has been found between T allele and HSIL, OR = 0.2121, [0.0473, 0.9517], p = 0.0866. Conclusion. No link has been found between VEGF +936 C/T and cervical intraepithelial neoplasia.

E-cadherin-160 C/A genotypes and cervical intraepithelial neoplasia.

PURPOSE: E-cadherin is a transmembrane glycoprotein with important roles in the maintenance of cervical squamous epithelium integrity. The purpose of this study was to investigate the relationship between E-cadherin-160 C/A polymorphism and cervical intraepithelial neoplasia (CIN). METHODS: A case-control study was performed enrolling 70 CIN cases and 107 age-matched healthy controls. Each patient was examined colposcopically, having a cervical specimen. All patients and controls have been genotyped for E-cadherin-160. Data were analysed using odds ratios (OR) and chi-square test at a significance level of p<0.005. RESULTS: The presence of E-cadherin-160 C/A was significantly associated with high-grade squamous intraepithelial lesion (HSIL) (OR=2.7916, 95% CI 1.1495,6.9345, x2=6.33, p=0.0118) and carcinoma in situ (CIS) (OR=2.5617, 95% CI 1.1676,5.6705, x2=6.63, p=0.0100). The detection of either CA or AA genotype was also significantly associated with HSIL and CIS. CONCLUSION: E-cadherin-160 genotype represents a valid risk factor for HSIL and CIS.