Impact of cord entanglement on perinatal outcome.

OBJECTIVE: To evaluate the impact of umbilical cord entanglement around various fetal organs on perinatal outcomes. STUDY DESIGN: A retrospective population-based study of all deliveries between 1988 and 2016 at a tertiary medical center. Immediate perinatal outcomes of newborns with and without cord entanglement were compared. RESULTS: The prevalence of any cord entanglement in our population was 16.62 % (45,312 cases out of 272,713 deliveries during the study period). Cord entanglement was found to be significantly associated with antepartum fetal death (OR = 2.13, 95 % CI 1.77-2.57, p < 0.001) and one-minute Apgar score less than 7 (OR = 1.21, 95 % CI 1.16-1.27, p < 0.001). There was no association between cord entanglement and small for gestational age (SGA) babies. CONCLUSION: Cord entanglement is associated with antepartum fetal death, but not with SGA.

Cord Blood Cell-Free DNA Concentration: A Novel Marker for Neonatal Wellbeing.

OBJECTIVE: Cord gas values and Apgar scores, currently used as markers for newborn wellbeing and postpartum complications, provide rough estimates, and their use remains elusive. Circulating cell-free DNA (cfDNA) may better represent newborn status at birth and the effect of parturition on the fetus. This pilot study investigates the association between cord blood (CB) cfDNA and neonatal outcomes. STUDY DESIGN: In a prospective cohort study, cfDNA concentration was measured in immediately following delivery collected CB sera of newborns using our rapid fluorescent assay. RESULTS: During the study period, blood samples from umbilical cords of 100 newborns were collected. Vaginal delivery was associated with a higher median CB cfDNA than cesarean delivery (277 [95% confidence interval [CI] 199-377] vs. 100 [95% CI 43-265] ng/mL, p < 0.01). cfDNA levels were significantly associated with gestational age at delivery (rho = 0.308, p = 0.002) and CB base deficit (BD, r = 0.252, p = 0.017). According to maternal and fetal complications, CB cfDNA was elevated in fetuses with category II of heart rate tracing (p < 0.05), with maternal positive vaginal culture (p < 0.01), and with premature rupture of membranes (PROM, p < 0.001). Logistic regression models of CB cfDNA fourth quartiles demostrate a double odds ratio for elevated BD (>3mmol/L) and for worse heart rate tracing category. CONCLUSION: Serum CB cfDNA concentration reflects the newborn's status and hazards with an excellent association with CB BD, fetal heart rate category, and maternal risk factors for infection (positive vaginal culture and PROM). This preliminary observation suggests that cfDNA can serve as a point of care biomarker for newborn status at the time of delivery. KEY POINTS: · CB cfDNA levels correlated with newborn's BD.. · CB cfDNA levels reflect parturition stress and inflammation.. · cfDNA serve as a diagnostic and prediction tool for the identification of newborns at risk for morbidity..

Placental abruption as a trigger of DIC in women with HELLP syndrome: a population-based study.

BACKGROUND: Disseminated Intravascular Coagulation (DIC) is a life-threatening condition. Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is one of the obstetrical syndromes mostly associated with DIC and thus, high rates of fatal complications. There is a lack of information regarding epidemiologic and clinical characteristics of women who developed HELLP syndrome with and without DIC. Additionally, until now, there is no adapted and widely accepted way to diagnose DIC among pregnant women presenting with HELLP syndrome, despite the evident maternal mortality linked to the disease.Objectives: (1) Address the gaps in knowledge regarding the prevalence, epidemiologic and clinical characteristics of women with HELLP syndrome who develop DIC; and (2) determine the risk factors for the development of DIC among women with HELLP syndrome. STUDY DESIGN: This was a population-based retrospective cohort study, including all women who delivered at the Soroka University Medical Center between the years 2001-2017. The study population was divided into three groups: (1) comparison group (n = 207,266 deliveries); (2) HELLP syndrome without DIC (n = 320); (3) HELLP syndrome with DIC (n = 21). The diagnosis of DIC was based on the ICD-9 code as recorded in the obstetrical database of the Soroka University Medical Center. The coding is based on the diagnosis made by the attending physician during hospitalization. RESULTS: (1) The rate of HELLP syndrome in the study population was 0.16% (341/207,607), of them 6.16% (21/341) had DIC; (2) among patients with HELLP syndrome, those with DIC had a higher median gravidity and parity; (3) a higher rate of severe maternal morbidity including blood product transfusion, placental abruption, eclampsia, acute renal failure and maternal death was observed in those who had HELLP syndrome and DIC compared to those with HELLP syndrome without DIC and the comparison group (p-value <.001 for comparison among the three groups); (4) among women with HELLP syndrome, those with DIC had a longer median PT difference, higher serum creatinine and lower AST as well as ALT median concentrations than those without DIC; (5) patients with HELLP syndrome and DIC had a higher rate of stillbirth and postpartum death than patients in the other groups (p-value <.001 for comparison among the three groups); and (6) placental abruption was an independent risk factor for the development of DIC in women with HELLP syndrome (p-value <.001). CONCLUSIONS: (1) Among women with HELLP syndrome, those who developed DIC had a higher rate of maternal and neonatal morbidity and mortality than those without DIC; and (2) placental abruption, but not abnormal liver function, was an independent risk factor for the development of DIC in women with HELLP syndrome.

Nonovert disseminated intravascular coagulation (DIC) in pregnancy: a new scoring system for the identification of patients at risk for obstetrical hemorrhage requiring blood product transfusion.

BACKGROUND: Nonovert disseminated intravascular coagulation (DIC) is a subclinical hemostatic dysfunction that has not yet reached the decompensation stage. The detection of pregnant patients at this stage may assist in the identification of those who will develop severe obstetrical hemorrhage, as it is one of the leading causes for preventable maternal mortality. Currently, nonovert DIC is diagnosed by a scoring system based on nonpregnant patients, originally generated by the International Society on Thrombosis and Hemostasis (ISTH), which does not address the physiologic changes of the hemostatic system during pregnancy. OBJECTIVES: (1) To develop a pregnancy-specific nonovert DIC score, (2) to determine the diagnostic performance of this score in detecting women at risk for obstetrical hemorrhage requiring blood product transfusion, and (3) to compare it to the existing ISTH nonovert DIC score. STUDY DESIGN: This retrospective study has longitudinal and cross-sectional components and includes three steps: (1) characterization of the longitudinal changes in the components of modified ISTH nonovert DIC scores, including these parameters - fibrinogen, antithrombin III, protein C, prothrombin time (PT), platelets, thrombin-antithrombin (TAT) complex, and D-dimer - during gestation in a group of normal pregnancies (n = 50); (2) development of a pregnancy-specific nonovert DIC score in a cross-sectional design of high-risk (n = 152) and control (n = 50) pregnancies, based on the predictive performance of each analyte for the detection of women at risk for obstetrical hemorrhage requiring blood product transfusion and a logistic regression model; and (3) comparison between the diagnostic performance of the pregnancy-specific nonovert DIC score and the modified ISTH nonovert DIC score to detect, upon admission, women who are at increased risk for subsequent development of obstetrical hemorrhage requiring blood product transfusion. RESULTS: (1) The study cohort included 202 patients, of which 21 (10%) had obstetrical hemorrhage that required blood product transfusion and were considered to have nonovert DIC; (2) using the nonpregnant ISTH nonovert DIC score, 92% of the patients had a D-dimer concentration above the 0.5 mg/L threshold, and only 2% were identified to have a low fibrinogen concentration (<100 mg/dL); thus, this scoring system was unable to identify any of the patients with nonovert DIC based on the suggested cutoff of a score of ≥5; (3) the parameters included in the pregnancy-specific nonovert DIC score were selected based on their contribution to the performance of the model for the prediction of women at risk for obstetrical hemorrhage requiring blood product transfusion; as a result, we excluded the PT difference parameter from the score and the TAT complex concentration was added; and (4) a pregnancy-specific nonovert DIC score of ≥3 had a sensitivity of 71.4% and a specificity of 77.9% to identify patients at risk for obstetrical hemorrhage requiring blood product transfusion. CONCLUSION: We propose (1) a pregnancy-specific nonovert DIC score adjusted for the physiologic changes in the hemostatic system during gestation; and (2) that the pregnancy-specific nonovert DIC score can be a useful tool for the identification of patients at risk for obstetrical hemorrhage requiring blood product transfusion.

S100B in maternal circulation of pregnancies complicated by FGR and brain sparing.

OBJECTIVE: To determine whether the presence of brain sparing in fetal growth restricted (FGR) fetuses involves elevation of the cerebral injury biomarker S100B in maternal circulation. METHODS: We included 63 women with suspected small for gestational age (SGA) fetuses between 24 and 35 +6/7 weeks of gestation. Maternal plasma angiogenic factors measurements and sonographic evaluation were performed at recruitment. Next, we subdivided our SGA cohort into three groups: SGA fetuses, FGR fetuses without brain-sparing, and FGR fetuses with brain-sparing (FGR-BS). Serum S100B concentration was calculated as S100B µg/L, S100B MoM, and the ratio S100B/ estimated fetal weight (EFW). We also report one case of S100B concentration surge in maternal serum following the diagnosis of fetal intraventricular hemorrhage (IVH). RESULTS: The FGR-BS group had higher maternal S100B µg/L (p < 0.01, p < 0.05, respectively), S100B MoM (p < 0.001, p < 0.001, respectively), and S100B/EFW (p < 0.001, p < 0.01, respectively), compared to the SGA and FGR groups. In the case report, maternal serum S100B concentrations were 0.0346 µg/L before, and 0.0874 µg/L after IVH occurrence. CONCLUSIONS: S100B concentration in maternal serum increased in pregnancies complicated by FGR and brain sparing. These results may substantiate in-utero cerebral injury and may explain the adverse neurocognitive outcomes reported for this group.

Fetal wide subarachnoid space and its outcome in cases of macrocephaly without ventriculomegaly.

Objective: To examine the occurrence and outcomes of fetuses with wide subarachnoid space (WSS) without ventriculomegaly in pregnant women with fetal macrocephaly as a sole diagnosis.Study design: A retrospective study was performed, analyzing patients with fetal macrocephaly between the years 2008 and 2018. All these patients underwent MRI, in order to detect brain anomalies. In the absence of any other brain abnormality, they were evaluated for WSS and their offspring's database was followed for at least two years after birth.Results: Ten patients were found to be carrying fetuses with macrocephaly, nine of them were diagnosed with WSS without ventriculomegaly prior to delivery. Following at least two years of follow up, all patients did not present significant neurodevelopmental abnormalities, apart from one child that had a genetic mutation of 15q21.2-22.31 deletion with other anomalies that were not diagnosed prenatally.Conclusions: We present herein for the first time in the literature a cohort of patients with a prenatal diagnosis of WSS without ventriculomegaly in fetuses with macrocephaly. Our data show that, in the presence of normal anomaly scan and normal chromosomal study, there is a low chance for significant neurodevelopmental abnormalities in fetuses with WSS without ventriculomegaly.

Estimation of fetal weight using Hadlock's formulas: Is head circumference an essential parameter?

OBJECTIVES: To test the equivalence of two fetal weight estimation formulas generated by Hadlock, a formula that includes head circumference parameter (H1), and another (H2) which excludes this parameter. A secondary aim was to identify the patients in which H2 formula is less reliable to use. STUDY DESIGN: This retrospective cohort study included a total of 1220 sonographic fetal weight estimations performed within seven days of delivery and recorded at a single medical center from January 2014 to December 2016. Estimated fetal weight was calculated using H1 and H2 formulas. Their accuracies were compared using percentage error, the proportion of weight estimations falling within ±15% error interval and by Bland-Altman analysis. Multivariate regression was performed to evaluate factors affecting weight estimation by H2 formula. RESULTS: The mean birth weight was 3288.92 ±â€¯641.27gr. The H2 formula presented with statistically significant higher value of systemic mean percent error comparing to H1 (3.19% vs. 1.87%, p < 0.001 respectively). H2 formula had a lower accuracy compared to H1 in predicting fetal weight within ±15% of birth weight (90.49% vs. 93.44%, p < 0.01 respectively). Using Bland-Altman analysis, the 95% limits of agreement between both formulas were (-142.03) to 231.79gr with a mean of 44.88gr. Factors found to influence significantly on H2 formula were long femur length (OR 1.144, p < 0.0001) and low maternal age (OR 0.947, p < 0.01). CONCLUSIONS: H1formula was more accurate than H2 formula in predicting fetal weight at term. However, the accuracy difference was found to be small. Therefore, if ultrasonographic evaluation of HC is technically difficult, Hadlock formula that excludes head circumference can be used with confidence. Caution should be paid with higher values of femur length and lower maternal age.

The prediction of early preeclampsia: Results from a longitudinal proteomics study.

OBJECTIVES: To identify maternal plasma protein markers for early preeclampsia (delivery <34 weeks of gestation) and to determine whether the prediction performance is affected by disease severity and presence of placental lesions consistent with maternal vascular malperfusion (MVM) among cases. STUDY DESIGN: This longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman. The abundance of 1,125 proteins was measured using high-affinity aptamer-based proteomic assays, and data were modeled using linear mixed-effects models. After data transformation into multiples of the mean values for gestational age, parsimonious linear discriminant analysis risk models were fit for each gestational-age interval (8-16, 16.1-22, 22.1-28, 28.1-32 weeks). Proteomic profiles of early preeclampsia cases were also compared to those of a combined set of controls and late preeclampsia cases (n = 76) reported previously. Prediction performance was estimated via bootstrap. RESULTS: We found that 1) multi-protein models at 16.1-22 weeks of gestation predicted early preeclampsia with a sensitivity of 71% at a false-positive rate (FPR) of 10%. High abundance of matrix metalloproteinase-7 and glycoprotein IIbIIIa complex were the most reliable predictors at this gestational age; 2) at 22.1-28 weeks of gestation, lower abundance of placental growth factor (PlGF) and vascular endothelial growth factor A, isoform 121 (VEGF-121), as well as elevated sialic acid binding immunoglobulin-like lectin 6 (siglec-6) and activin-A, were the best predictors of the subsequent development of early preeclampsia (81% sensitivity, FPR = 10%); 3) at 28.1-32 weeks of gestation, the sensitivity of multi-protein models was 85% (FPR = 10%) with the best predictors being activated leukocyte cell adhesion molecule, siglec-6, and VEGF-121; 4) the increase in siglec-6, activin-A, and VEGF-121 at 22.1-28 weeks of gestation differentiated women who subsequently developed early preeclampsia from those who had a normal pregnancy or developed late preeclampsia (sensitivity 77%, FPR = 10%); 5) the sensitivity of risk models was higher for early preeclampsia with placental MVM lesions than for the entire early preeclampsia group (90% versus 71% at 16.1-22 weeks; 87% versus 81% at 22.1-28 weeks; and 90% versus 85% at 28.1-32 weeks, all FPR = 10%); and 6) the sensitivity of prediction models was higher for severe early preeclampsia than for the entire early preeclampsia group (84% versus 71% at 16.1-22 weeks). CONCLUSION: We have presented herein a catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes. The sensitivity of maternal plasma protein models for early preeclampsia is higher in women with underlying vascular placental disease and in those with a severe phenotype.

Maternal total cell-free DNA in preeclampsia and fetal growth restriction: Evidence of differences in maternal response to abnormal implantation.

OBJECTIVES: Preeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR). STUDY DESIGN: A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis. RESULTS: Women with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400-2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0-1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72-2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144-1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025). CONCLUSIONS: Preeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR.

The risk of placenta accreta following primary cesarean delivery.

OBJECTIVE: To (a) evaluate the risk for placenta accreta following primary cesarean section (CS), in regard to the stage of labor, the cesarean section was taken (elective prelabor vs. unplanned during labor); and (b) investigate whether the association between placenta accreta and maternal and neonatal complications is modified by the type of the primary CS. STUDY DESIGN: In a population-based retrospective cohort study, we included all singleton deliveries occurred in Soroka University Medical Center between 1991 and 2015, of women who had a history of a single CS. The deliveries were divided into three groups according to the delivery stage the primary CS was carried out: 'Unplanned 1' (first stage-up to 10 cm), 'Unplanned 2' (second stage-10 cm) and 'Elective' prelabor CS. We assessed the association between the study group and placenta accreta using logistic generalized estimation equation (GEE) models. We additionally assessed maternal and neonatal complications associated with placenta accreta among women who had elective and unplanned CS separately. RESULTS: We included 22,036 deliveries to 13,727 women with a history of one CS, of which 0.9% (n = 207) had placenta accreta in the following pregnancies: 12% (n = 25) in the 'Unplanned 1' group, 7.2% (n = 15) in the ' Unplanned 2' group and 80.8% (n = 167) in the 'elective' group. We found no difference in the risk for subsequent placenta accreta between the groups. In a stratified analysis by the timing of the primary cesarean delivery, the risk for maternal complications, associated with placenta accreta, was more pronounced among women who had an unplanned CS (OR 27.96, P < 0.01) compared to women who had an elective cesarean delivery (OR 13.72, P < 0.01). CONCLUSIONS: The stage in which CS is performed has no influence on the risk for placenta accreta in the following pregnancies, women who had an unplanned CS are in a higher risk for placenta accrete-associated maternal complications. This should be taken into consideration while counselling women about their risk while considering trial of labor after cesarean section.

Dilated cerebral venous system observed in growth-restricted fetuses.

PURPOSE: The dilation of the fetal cerebral veins is a rare phenomenon that may be associated to a bad obstetric outcome, and is usually connected to antenatal thrombosis of the posterior dural venous sinuses. There are several descriptions of cerebral vein distension on magnetic resonance imaging (MRI), but all of them are detected postnatally. We present herein two cases of fetal antenatal cerebral dilation of the venous system, without any association to any sign of vein thrombosis, and a systematic review of literature regarding pathogenesis, diagnosis and outcomes associated to the antenatal detection of this condition with the use of MRI. MATERIALS AND METHODS: To identify potentially eligible studies, we searched PubMed, Scopus, Cochrane Library (all from inception to October 20th, 2016) and applied no language restrictions. RESULTS: The electronic database search provided a total of 22,843 results. After the exclusion of duplicates, manuscripts that resulted not relevant to the review based on title and abstract screening, and analysis of manuscripts eligible for full-text assessment, no papers were found related to the subject reported in the present manuscript. CONCLUSIONS: Our report adds importance to MRI as a tool in cases of complex ultrasound finding with the presence of fetal heart failure and deterioration of fetal growth, in order to improve the prognostic evaluation and patient?s counseling.

The more you lose the more you miss: accuracy of postpartum blood loss visual estimation. A systematic review of the literature.

Midwives and nurses have a key role in monitoring postpartum period. They represent the first line professional figure in quantifying blood loss, initiating early diagnosis of obstetric hemorrhage, and mobilizing a team response, if needed. These actions are crucial in determining maternal outcome in postpartum hemorrhage (PPH). In our review we aimed to: (1) Provide a picture of PPH including its pathophysiology, epidemiology, and associated complications; (2) Discuss diagnosis of this dangerous postpartum event; and, (3) Especially evaluate the efficiency of the employment of visual blood loss estimation as a rapid way to suspect PPH and activate the patient assessment.

Comparison of the Long-Term Oncological Outcomes of Stent as a Bridge to Surgery and Surgery Alone in Malignant Colonic Obstruction.

BACKGROUND: Self-expanding metallic stents (SEMS) insertion is an alternative to emergency surgery in malignant colonic obstruction. However, the long-term oncological outcome of stents as a bridge to surgery is limited and controversial. OBJECTIVES: To determine the long-term oncological outcome of stents as a bridge to surgery. METHODS: Data of patients who underwent emergency surgery and endoscopic stent insertion as a bridge to surgery due to obstructing colon cancer at Soroka Medical Center during a 14 year period were collected retrospectively. Preoperative data, tumor staging, and oncological outcomes in terms of local recurrence, metastatic spread, and overall survival of the patients were compared. RESULTS: Sixty-four patients (56% female, mean age 72 years) were included in the study: 43 (67%) following emergency surgery, 21 stent inserted prior to surgery. A stent was inserted within 24-48 hours of hospital admission. The mean time between SEMS insertion and surgery was 15 days (range 0-30). Most of the patients had stage II (41%) and stage III (34%) colonic cancer. There was no difference in tumor staging and localization between groups. There was no significant difference in disease recurrence between SEMS and surgery groups, 24% and 32%, respectively. Disease-free survival rates were similar between the SEMS group (23.8%) and surgery group (22%). Four year and overall survival rates were 52.4% vs. 47.6%, 33.3% vs. 39.5%, respectively. CONCLUSIONS: SEMS as a bridge to surgery in patients with obstructing colon cancer provide an equivalent long-term oncological outcome to surgery alone.

NKp44 and NKp30 splice variant profiles in decidua and tumor tissues: a comparative viewpoint.

NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-ß, IL-15 and IL-18 are able to influence both NKp44 and NKp30 splice variant profiles, leading to cytokine-associated profiles. Placenta and cancerous tissues have many similarities; both are immunologically privileged sites and both share immune tolerance mechanisms to support tissue development. Therefore, we studied the profiles of NKp44 and NKp30 splice variants in these states by comparing (i) decidua from pregnancy disorder and healthy gestation and (ii) matched normal and cancer tissue. Decidua samples had high incidence of both NKp44 and NKp30. In cancerous state it was different; while NKp30 expression was evident in most cancerous and matched normal tissues, NKp44 incidence was lower and was mostly associated with the cancerous tissues. A NKp44-1dominant inhibitory profile predominated in healthy pregnancy gestation. Interestingly, the NKp44-2/3 activation profile becomes the leading profile in spontaneous abortions, whereas balanced NKp44 profiles were observed in preeclampsia. In contrast, a clear preference for the NKp30a/b profile was evident in the 1st trimester decidua, yet no significant differences were observed for NKp30 profiles between healthy gestation and spontaneous abortions/preeclampsia. Both cancerous and matched normal tissues manifested balanced NKp30c inhibitory and NKp30a/b activation profiles with a NKp44-1dominant profile. However, a shift in NKp30 profiles between matched normal and cancer tissue was observed in half of the cases. To summarize, NKp44 and NKp30 splice variants profiles are tissue/condition specific and demonstrate similarity between placenta and cancerous tissues.

Ultrasonographic approach to diagnosis of fetal inflammatory response syndrome: a tool for at-risk fetuses?

Preterm parturition is a syndrome that may result from many underlying mechanisms. Infection and inflammation are the prominent ones. Intrauterine infection and inflammation have an effect akin to sepsis, and that is similar to systemic inflammatory response in adults. Indeed, there is evidence to support the association of a fetal inflammatory response syndrome (FIRS) to systemic infection and inflammation. The utilization of invasive procedures for the prenatal diagnosis of FIRS is associated with a risk for complications resulting from the invasive method. The progress in the imaging quality of obstetrical ultrasound and the development of novel methods for functional anatomical assessment of the fetal organs may help to identify, noninvasively, fetuses at risk for FIRS in patients presenting with preterm labor. We review the studies describing advanced sonographic modalities and the imaging findings in the heart, thymus, kidney, adrenal glands, and spleen of these fetuses.

Placental calcifications: a clue for the identification of high-risk fetuses in the low-risk pregnant population?

"What does it mean, Doctor?" and "Is it going to affect my baby in some way?". Those are the most typical questions of pregnant women to obstetricians. Answering is sometimes easier but placental calcification is not the case, since placental architecture and disease are two different faces of the same coin and the association between them is not completely clear. Placenta can function properly, even in the presence of architectural alterations, without any fetal consequences. So, remains the question, when does a placental structural anomaly become a sign of increased attention to maternal conditions, fetal development and well-being? The present review will analyze these concepts, with emphasis on placental calcification, its pathogenesis, and the state-of-the-art regarding the influence of this finding on pregnancy outcomes among low-risk pregnant patients.

First Trimester Pregnancy Loss and the Expression of Alternatively Spliced NKp30 Isoforms in Maternal Blood and Placental Tissue.

Capsule: We observed that first trimester pregnancy loss is associated with an altered expression profile of the three isoforms of the NK receptor NKp30 expressed by NKs in PBMC and placental tissue. In this study, we aimed to investigate whether first trimester pregnancy loss is associated with differences in expression of NKp30 splice variants (isoforms) in maternal peripheral blood or placental tissue. We conducted a prospective case-control study; a total of 33 women undergoing dilation and curettage due to first trimester pregnancy loss were further subdivided into groups with sporadic or recurrent pregnancy loss. The control group comprises women undergoing elective termination of pregnancy. The qPCR approach was employed to assess the relative expression of NKp30 isoforms as well as the total expression of NKp30 and NKp46 receptors between the selected groups. Results show that in both PBMC and placental tissue, NKp46 and NKp30 expressions were mildly elevated in the pregnancy loss groups compared with the elective group. In particular, NKp46 elevation was significant. Moreover, expression analysis of NKp30 isoforms manifested a different profile between PBMC and the placenta. NKp30-a and NKp30-b isoforms in the placental tissue, but not in PBMC, showed a significant increase in the pregnancy loss groups compared with the elective group. Placental expression of NKp30 activating isoforms-a and -b in the pregnancy loss groups was negatively correlated with PLGF expression. By contrast, placental expression of these isoforms in the elective group was positively correlated with TNFα, IL-10, and VEGF-A expression. The altered expression of NKp30 activating isoforms in placental tissue from patients with pregnancy loss compared to the elective group and the different correlations with cytokine expression point to the involvement of NKp30-mediated function in pregnancy loss.

The clinical utility of sonographic cervical length in the management of preterm parturition at 28-32 weeks of gestation.

OBJECTIVES: The aim of this study was to evaluate the role of cervical length measurement in early third trimester (28-32 weeks) as a predictor of preterm delivery (PTD), in women presenting with preterm parturition. METHODS: Cervical length was measured prospectively, in singleton pregnancies at 28-32 weeks with preterm contractions (PTC). A multivariate linear regression model was performed to assess the association between cervical length and gestational age at delivery. Logistic regression analysis with PTD before 34 and 37 weeks of gestation as the outcome variable was performed to control for confounders. RESULTS: Fifty-six women were included, mean gestational week at presentation and at delivery were 29.88 ± 1.13 and 37.05 ± 2.86, respectively. There was a direct association between short cervical length at admission and gestational week at delivery (p = 0.027). This association remained significant even after controlling for confounders. Short cervical length was significantly associated with PTD before 34 (p = 0.045) or 37 (p = 0.046) weeks of gestation. CONCLUSIONS: Third trimester cervical length measurement in patients with PTC is associated with gestational week at delivery, as well as PTD prior to 34 and 37 weeks of gestation. Therefore, examining cervical length is clinically valuable and probably cost-effective during early third trimester.

Hypothyroidism and diabetes mellitus - a risky dual gestational endocrinopathy.

Objectives. Diabetes mellitus (DM) and hypothyroidism are each associated with increased rate of pregnancy complications. However, their combined morbidity during gestation is poorly studied. Therefore, the aims of this study were to determine the prevalence of the combined morbidity of DM & hypothyroidism and whether it is associated with adverse maternal and neonatal outcome. Study design. This population based retrospective cohort study included 87,213 women who had 232,293 deliveries. All deliveries were divided into the following groups: (1) hypothyroidism & DM (n = 171); (2) hypothyroidism (n = 1502); (3) DM (n = 13,324); and (4) deliveries of women with neither endocrinopathy, who served as a control group (n = 217, 296). Results. The prevalence of DM & hypothyroidism in our population was 0.17%. In comparisons to the other study groups, women with DM & hypothyroidism had higher rates of infertility (p < 0.001), preeclampsia (p < 0.001), chronic hypertension (p < 0.001), preterm birth (p < 0.001), and cesarean deliveries (p < 0.001). In Generalized Estimating Equations (GEE) model, hypothyroidism & DM was an independent risk factor for cesarean section (OR 3.46; 95% CI 2.53-4.75) and for preeclampsia (OR 1.82; 95%CI 1.16-2.84). Conclusion. The combination of DM & hypothyroidism is rare, yet it is associated with higher rate of infertility, cesarean sections, preterm deliveries, and hypertensive disorders of pregnancy than the rest of the population. This dual endocrinological combination is an independent risk factor for preeclampsia and cesarean section. These findings suggest that these patients are at risk for perinatal complications and should be followed and delivered as high risk pregnancies.