Modified Myocardial Performance Index in Fetal Growth Disturbances as Diagnostic and Prognostic Adjunct.

BACKGROUND: Fetal growth disturbance can be associated with cardiac dysfunction. This study aimed to assess the modified myocardial performance index in growth-restricted and appropriate for gestational age fetuses and evaluate both its prognostic value in perinatal period and also its association with adverse perinatal outcomes. METHODS: Totally 131 pregnant women were included in this prospective study. Of these, 56 cases were in study group with a diagnosis of small fetus and 75 cases were in control group with a diagnosis appropriately grown fetus. Fetal echocardiography was performed in all pregnant women to measure modified myocardial performance index. Umbilical, middle cerebral and uterine artery Doppler ultrasound parameters were measured in the study group. Small fetuses were categorized into 2 subgroups of late-onset fetal growth restriction and small for gestational age. RESULTS: Modified myocardial performance index was significantly higher in small fetuses compared to controls (0.45 vs. 0.37, P <.001). Newborn intensive care unit admission rates were significantly higher in small fetuses than in controls (chi-square test, P <.001). The highest mean modified myocardial performance index was recorded in the late-onset fetal growth restriction subgroup (0.45 vs. 0.41 vs. 0.37). The sensitivity and specificity of modified myocardial performance index in predicting adverse outcomes at a cut-off value of 0.41 were 63% and 75%, respectively. There was a significant negative correlation between modified myocardial performance index values and birth weights. CONCLUSIONS: We found higher left fetal heart modified myocardial performance index values in small fetuses indicating the presence of prenatal cardiac dysfunction. Fetal myocardial performance deteriorates in concordance with severity of growth restriction. Modified myocardial performance index can also be used to predict adverse perinatal outcomes among growth-restricted fetuses.

Association between early oxidative DNA damage and iron status in women with gestational diabetes mellitus.

This study aims to assess the relationship between oxidative DNA damage and iron status in women with gestational diabetes mellitus (GDM) compared to those with normal glucose tolerance in the first and the second trimesters of pregnancy. Maternal serum and urine samples were collected in the 11th-14th weeks and the 24th-28th weeks of gestation. In addition to oral glucose tolerance test in the second trimester, fasting blood glucose, HbA1c, ferritin and hemoglobin levels were measured in blood samples. Urinary levels of oxidative DNA damage products 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and 8,5'-cyclo-2'-deoxyadenosines (S-cdA, R-cdA) were determined using liquid chromatography-tandem mass spectrometry with isotope-dilution. In the first trimester, urinary 8-OH-dG levels were found higher in the GDM group (n = 33) than in the control group (n = 84) (p = 0.006). R-cdA and S-cdA levels were not significantly different between the two groups (p = 0.794 and p = 0.792 respectively). When the cases were stratified according to their first trimester ferritin levels, women with ≥50th centile (≥130 ng/mL) demonstrated higher levels of 8-OH-dG and R-cdA than those under <50th centile (p = 0.034, p = 0.009). In the GDM group, there was a positive correlation between the second trimester 8-OH-dG and ferritin and 1st-hour glucose levels (p = 0.014, p = 0.020). This is the first study where oxidative DNA damage is evaluated in both early and late periods of pregnancy. Our findings reveal an association between GDM and iron status and oxidative DNA damage.

First-trimester placental function in levothyroxine-using pregnant women: a case-control study.

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.

Prediction of ischemic placental diseases during the first trimester combined test period: a retrospective cohort of low-risk pregnancies in search of the link between parity and disease.

Objective: To assess the predictive power of a multifactorial model established on maternal characteristics, placenta-associated plasma protein A (PAPPA), and the mean uterine artery pulsatility index (Ut A PI) levels for the development of ischemic placental diseases (IPD) during the first-trimester combined test (FTCT) period and to evaluate the strength of some generally accepted clinical risk factors.Method: The studied data were obtained from a retrospective cohort of low-risk singleton pregnancies in the FTCT between 1 August 2016 and 1 December 2017. After routine 11-13-week examinations for FTCT, the Ut A PI was measured and stored electronically. The PAPPA multiple of median (MoM) was obtained as a routine component of aneuploidy screening.Results: A sample of 2493 pregnancies with clearly documented outcomes was studied. Early-onset preeclampsia, late-onset preeclampsia and fetal growth restriction (FGR) were observed in 9 (0.36%), 27 (1.08%), and 41 (1.64%) cases, respectively. With optimum cut-off levels of 0.69 for PAPPA MoM and 2.05 for mean Ut A PI and a false positive rate of 4.9%, IPD cases could be predicted with 83.3% sensitivity and 73.7% specificity. Nulliparity, previous abortion in nulliparous women and first pregnancy from second marriage were not independent risk factors. Maternal age, an interval from the last delivery longer than 6 years, and body mass index were found to be independent risk factors.Conclusion: The IPD showed some common and distinct clinical, laboratory and Doppler findings during the FTCT and were predictable with the help of multifactorial analysis. Some widely accepted risk factors could be affected by various confounders. Because of the increased IPD frequencies, parous women with a time interval from the last delivery of 6 years or longer should be screened as a high-risk group for placental dysfunction-related diseases.

A prospective cohort study on the prediction of the diagnosis-to-delivery time in preeclamptic pregnancies: should the sFlt-1/PlGF ratio be added to routine evaluations?

PURPOSE: To analyze the clinical and laboratory factors that potentially affect the diagnosis-to-delivery time in preeclamptic pregnancies. METHODS: In this cross-sectional study, we followed 24 early onset preeclampsia (E-PE) and 26 late-onset preeclampsia (L-PE) cases. Maternal serum samples were obtained at the time of diagnosis and stored at - 80 °C until ELISA analysis for soluble fms-like tyrosine kinase-1 (SFlt-1) and placental growth factor (PlGF) levels. RESULTS: The median follow-up duration was 68 (1-339) h in the E-PE group and 330 (7-1344) h in the L-PE group. Maternal mean arterial pressure (MAP) at hospitalization was the strongest variable, and the sFlt-1/PlGF ratio added significantly to the Cox regression model. In the E-PE cases, the median sFlt-1/PlGF ratio was significantly higher in the subgroup with a follow-up duration > 48 h than in the subgroup of cases with a follow-up duration ≤ 48 h (5109 vs. 2080; p = 0.038), and none of the seven cases with an sFlt-1/PlGF ratio ≥ 75th percentile delivered during the first 48 h. Neither the 24-h proteinuria nor the gestational age at diagnosis added to the predictive power of the MAP at hospitalization. CONCLUSION: Incorporation of the sFlt-1/PlGF ratio to the routine evaluation of preeclamptic pregnancies may help in the prediction of progression and management planning.

Predictability of myometrial, lower uterine segment and cervical invasion with 3D transvaginal ultrasonography and magnetic resonance imaging in endometrial cancer patients: a prospective cohort study.

AIMS: The objective of this study is to identify the diagnostic performance of three-dimensional transvaginal ultrasonography (3D-US) and magnetic resonance imaging (MRI) in detecting myometrial, lower uterine segment and/or cervical invasion in endometrial cancer patients. MATERIALS AND METHODS: In this prospective study, 40 patients diagnosed with endometrial cancer were performed 3D-US and MRI, preoperatively. Deep myometrial, lower uterine segment and cervical invasion were evaluated subjectively and results were compared with the final histology as a gold standard. RESULTS: Diagnostic accuracy of 3D-US for detecting deep myometrial, lower uterine segment and cervical invasion were 87.5%, 80% and 85%, respectively. The same results for MRI were 75%, 65% and 70%, respectively. For deep myometrial, lower uterine segment and/or cervical invasion in endometrial cancer, 3D-US had higher sensitivity, specificity, negative and positive predictive value and accuracy than MRI. The combination of these two imaging techniques had an increased sensitivity of detecting all parameters related with tumoral invasion but decreased specificity and the accuracy. CONCLUSION: 3D-US had better performance in detecting myometrial, lower uterine segment and/or cervical invasion than MRI in endometrial cancer patients. Combination of these techniques was not preferred according to this study.

The protective effect of Gingko biloba in a rat model of ovarian ischemia/reperfusion injury: Improvement in histological and biochemical parameters.

BACKGROUND: Ovarian torsion is one of the most common gynecological emergencies, which especially affects women of reproductive age. OBJECTIVES: We aimed to evaluate the effect of Ginkgo biloba (GB) supplementation in ovarian ischemia/ reperfusion injury in an experimental torsion/de-torsion rat model. MATERIAL AND METHODS: This study was carried out in the Ege University Faculty of Medicine in Izmir, Turkey. Thirty mature female Sprague-Dawley albino rats were randomly divided into 5 groups: in Group 1 (control), the abdominal wall was only opened and closed; in the torsion group (Group 2), ischemia was induced for 3 h, using atraumatic vascular clips to create a torsion model; in the torsion/GB group (Group 3), the rats were given 80 mg/kg (oral gavage) of GB 30 min before torsion was induced and the torsion model was formed; in the torsion/de-torsion group (Group 4), the rats underwent 3 h of ischemia and then the vascular clips were removed and reperfusion took place for 3 h; in the torsion/de-torsion/GB group (Group 5), the rats underwent 3 h of ischemia followed by GB (oral gavage) 30 min prior to a 3-h reperfusion period. Ovarian tissue damage was evaluated by a histopathological scoring system. Ovarian tissue malondialdehyde (MDA) and plasma pentraxin-3 were measured. RESULTS: In comparison with the sham group, both the torsion and torsion/de-torsion groups had significantly higher scores for follicular degeneration, vascular congestion, edema, hemorrhage, and leukocyte infiltration. Ginkgo biloba significantly decreased these scores in both groups. Ovarian malondialdehyde and plasma pentraxin 3 were significantly higher both in the torsion and torsion/de-torsion groups compared with the sham group. Ginkgo biloba decreased these levels significantly both in the torsion/GB and torsion/de-torsion/GB groups. CONCLUSIONS: Supplementing GB during a surgical procedure decreases ischemia/reperfusion injury to an ovary in an experimental rat model based on histopathological parameters, tissue malondialdehyde, and plasma pentraxin-3 levels.

A prospective study on fetal posterior cranial fossa assessment for early detection of open spina bifida at 11-13 weeks.

The objective of this study was to test three measurements: brain stem (BS), intracranial translucency (IT) and brain stem to occipital bone distance (BSOB), as well as one landmark: cisterna magna (CM) visibility, for early diagnosis of open spina bifida (OSB) in a low risk population. A prospective observational study was undertaken in a university hospital. A sample of 1479 women consented to participate between 20 September 2013 and 30 June 2015. Measurements were performed from the mid-sagittal view, as is routinely used for nuchal thickness assessment. CM visibility was assessed qualitatively as the third anechoic band in the posterior cranial fossa (PCF). All pregnancies were screened with a combination of maternal serum alpha-fetoprotein and second trimester anomaly scan and followed until delivery. Predictive values were calculated for each marker. We were able to diagnose two OSB cases and highly suspect one Dandy-Walker malformation case at the first trimester scan by the observation of PCF. PCF characteristics of OSB cases were increased BS diameter, increased BS-BSOB ratio and non-visualization of the CM. All the markers demonstrated high sensitivity and specificity but CM visibility reached the highest positive predictive value. Due to relatively high false positive rates, PCF measurements could not reach a satisfactory performance to validate their clinical use as a single marker. CM visibility has the advantage of being a qualitative marker and reduces the need for sophisticated and time-consuming measurements. Intracranial translucency and BS-BSOB ratio measurements should be used when the CM visibility is absent or in doubt.

Pendrin Expression in Preeclampsia: A Prospective Immunohistochemical Staining Study on Placental Bed Biopsies.

INTRODUCTION: To assess the pendrin expression density in placental bed biopsies from preeclampsia cases in comparison with healthy term controls. MATERIAL AND METHODS: A prospective case-control study with 106 placental bed biopsies obtained during cesarean deliveries. Pendrin expression was evaluated by immunohistochemical staining in different hypertensive disorders of pregnancy. RESULTS: Pendrin immunostaining frequency was higher in the hypertensive disorders group (p: 0.024), which was a result of the high frequency in the early-onset preeclampsia group. Uterine artery pulsatility indices were higher in pendrin positive patients than in the negatives in the case group. Gravidity was not found to affect the pendrin expression frequency in the placental bed. CONCLUSION: Placental ischemia seems to be an important determinant of pendrin expression in pregnant decidua. Increased pendrin density in early-onset preeclampsia could be a pathogenetic mechanism in or a part of the adaptational response to the development of the hypertension.

A prospective cohort study on the prediction of fetal distress and neonatal status with arterial and venous Doppler measurements in appropriately grown term fetuses.

PURPOSE: To assess the predictive power of the cerebro-placental ratio (CPR) and the venous-arterial index (VAI) for the development of intrapartum fetal distress (FD) and neonatal intensive care unit (NICU) admission. METHODS: Fetal umbilical artery, middle cerebral artery and umbilical vein Doppler measurements were obtained before the active phase of labor in 311 singleton pregnancies at ≥37 weeks. A continuous electronic fetal monitorization was applied, and an umbilical cord blood sample was obtained for each participant. FD and NICU admission were the primary outcomes. RESULTS: Labor was concluded as uncomplicated spontaneous vaginal delivery (SVD) in 261 (83.9%) cases. The 22 (7.1%) FD cases were subdivided into FD with NICU admission (n: 7; 2.3%) and without NICU admission (n: 15; 4.8%). Six out of 7 (85.8%) FD with NICU admission cases were from nulliparous pregnancies. The combinatory indices (VAI and CPR) reached the highest sensitivity (31.8%) and negative predictive value (94.7%). None of the fetuses, distressed or non-distressed, with CPR ≤ 10th percentile was born with a cord pH < 7.20. CONCLUSION: FD frequency was increased in fetuses with a low CPR or low VAI. However, the Doppler patterns were heterogeneous in both subgroups: FD with and without NICU admission. FD seems to be a common endpoint of different circulatory-metabolic disturbances. Parity affects the FD frequency in a manner related but not limited to fetal arterial and venous circulation. Low CPR could be a part of the adaptive mechanisms providing metabolic preparedness for hypoxic episodes.

A prospective study on first trimester prediction of ischemic placental diseases.

OBJECTIVE: The objective of the study is to assess the predictive power of mean uterine artery pulsatility index (UtA PI), maternal serum placental growth factor (PlGF) and placenta associated plasma protein A levels for the development of ischemic placental diseases (IPD) in a cohort of unselected singleton pregnancies during the first trimester combined test period. MATERIALS AND METHODS: A sample of 880 pregnancies was registered between September 2014 and January 2016. After routine examination for first trimester combined test, UtA PI was measured, and maternal serum was obtained and stored at -80 °C for PlGF assessment. RESULTS: Early-onset preeclampsia, late-onset preeclampsia and placental dysfunction-related fetal growth restriction were observed in 6 (0.7%), 17 (2.0%) and 27 (3.2%) cases, respectively. IPD requiring delivery before 34 weeks of gestation could be predicted with a sensitivity, specificity, positive predictive value and negative predictive value of 76.2%, 90.2%, 20.2% and 99.1%, respectively. CONCLUSION: A combination of UtA PI, placenta associated plasma protein A and PlGF was proven to be successful in the first trimester prediction of IPD, with the highest sensitivity in the subgroup who required delivery before 34 weeks of gestation. In reducing the number of pregnancies that should be followed-up, further studies for new biomarkers are needed. © 2017 John Wiley & Sons, Ltd.

Analysis of first-trimester combined test results in preparation for a cell-free fetal DNA era.

OBJECTIVE: To survey experience with the first-trimester combined test (FCT) for trisomy 21 (T21) in different risk score groups to determine the most useful clinical application of cell-free fetal DNA (cffDNA) screening. METHODS: In a retrospective study, the records of FCT results obtained at a center in Turkey between January 2009 and January 2014 were reviewed. The FCT results and rates of uptake of invasive diagnostic testing were compared among different risk score groups. RESULTS: FCT results were available for 4804 pregnancies; 276 (5.7%) had IDT results. Ten (72.7%) of 11 cases of T21 had a risk score of 1:300 or more. The IDT uptake rates were 54.5%, 51.9%, and 47.4% at risk scores of 1:100 or more, 1:200 or more, and 1:300 or more, respectively. In the group at intermediate risk (1:1001-1:3000), no pregnancy had an FCT result of both low pregnancy-associated plasma protein A and high free ß-human chorionic gonadotropin, but 30 (3.9%) of 766 pregnancies had both advanced maternal age and high ß-human chorionic gonadotropin. CONCLUSION: cffDNA screening should be used to optimize IDT uptake in pregnancies with a risk score of 1:101-1:1000. The selective power of the FCT diminishes beyond the 1:1001 score and cffDNA screening cannot yet be recommended routinely.

Termination of pregnancy for fetal abnormalities: main arguments and a decision-tree model.

INTRODUCTION: By looking through our ethical committee cases, we demonstrate the main arguments we use for making a judgment in face of fetal abnormalities. Our decision making model is a simplified algorithm of the arguments and concepts we use in scientific-ethic discussion. MATERIALS AND METHODS: A retrospective analysis was conducted from single, tertiary referral center of patients evaluated for fetal abnormalities from 2004 to 2014. We hypothesized that all our judgments would fit into a decision-tree model. RESULTS: 553 fetal abnormality cases were discussed, 348 (63%) were given termination of pregnancy (TOP) proposal. When detected <24 weeks, fetuses with chromosomal abnormality/genetic disorders (n:100) and with mental retardation risk (n:93) ended up with TOP proposal. For incompatibility with life cases (n:111) and the multimorbidity cases (n:44) the committee suggest TOP, regardless of gestational age. The highest family approval ratios were in chromosomal abnormalities/genetic disorders group (93%), and the lowest figures were in mental retardation risk group (80%). DISCUSSION: Continuously changing literature on prenatal and postnatal therapy options and the long term outcome of various fetal abnormalities influence committee decisions. Theoretical high success rates and inconsistent data on long term prognosis of some anomaly groups resulted in heterogenous decisions and various approval ratios.