SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells.

BACKGROUND: Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. METHODS: In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. RESULTS: S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1ß formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1ß. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. CONCLUSION: S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video Abstract.

Prenatal Management and Perinatal Outcome in a Large Series of Hydrops Fetalis.

INTRODUCTION: Nonimmune hydrops fetalis (NIHF) is the most frequent etiology of hydrops fetalis (HF), accounting for around 95% of cases. It associates high perinatal mortality and morbidity rates. The aim of the study was, first, to investigate etiology, prenatal management, and perinatal outcome in a large single-center series of HF; second, to identify prenatal prognostic factors with impact on perinatal outcome. MATERIALS AND METHODS: Observational retrospective study of 80 HF diagnosed or referred to a single tertiary center between 2012 and 2021. Clinical characteristics, etiology, prenatal management, and perinatal outcome were recorded. Adverse perinatal outcome was defined as intrauterine fetal death (IUFD), early neonatal death (first 7 days of life) and late neonatal death (between 7 and 28 days). RESULTS: Seventy-six of the 80 cases (95%) were NIHF, main etiology being genetic disorders (28/76; 36.8%). A total of 26 women (32.5%) opted for termination of pregnancy, all of them in the NIHF group. IUFD occurred in 24 of 54 patients (44.4%) who decided to continue the pregnancy. Intrauterine treatment was performed in 29 cases (53.7%). There were 30 newborns (55.6%). Adverse perinatal outcome rate was 53.7% (29/54), significantly higher in those diagnosed <20 weeks of gestation (82.4% < 20 weeks vs. 40.5% ≥ 20 weeks; p = 0.004). Survival rate was higher when fetal therapy was performed compared to the expectantly managed group (58.6% vs. 32%; p = 0.05). Intrauterine blood transfusion and thoraco-amniotic shunt were the procedures that achieved the highest survival rates (88.9% and 100%, respectively, p = 0.003). CONCLUSION: NIHF represented 95% of HF with genetic disorders as the main etiology. Most of them were diagnosed before 20 weeks of gestation, with worse prognosis than cases detected later in gestation. Rates of TOP, IUFD, and early neonatal death were higher in NIHF. Intrauterine therapy, when indicated, improved the perinatal outcome.

The influence of air pollution on gestational age at delivery and birthweight in patients with or without respiratory allergy: A nested case-control study.

INTRODUCTION: Air pollution is a current major health issue. The burden of airborne pollutants and aeroallergen levels varies throughout the year, as well as their interaction and consequences. Prenatal exposure during pregnancy has been associated with adverse perinatal outcomes. The aim of this study was to evaluate the impact of air pollutants on perinatal outcomes in patients with or without respiratory allergy. MATERIAL AND METHODS: Nested case-control retrospective study on 3006 pregnant women. Correlations between concentrations of common pollutants in each trimester of pregnancy and on average during the whole pregnancy and both gestational age at delivery and birthweight were studied. Pearson's correlation coefficient and binary logistic regression were used. RESULTS: In general, pollutants correlated more strongly with birthweight than with gestational age at delivery. Nine-month NO2 , SO2 , CO, and benzene, and second-trimester CO negatively correlated with birthweight, whereas only first-trimester NO2 showed a very mild correlation with gestational age at delivery. Negative correlations between pollutants and birthweight were much stronger in the respiratory allergy group (n = 43; 1.4%) than in the non-allergic group. After adjustments, the most significant predictive pollutant of birthweight was SO2 in both groups. The best predictive model was much stronger in the allergic group for third-trimester SO2 (R2 = 0.12, p = 0.02) than in the non-allergic group for total SO2 (R2 = 0.002, p = 0.02). For each unit that SO2 increased, birthweight reduced by 3.22% vs. 1.28% in each group, respectively. CONCLUSIONS: Air pollutant concentrations, especially SO2 , negatively influenced birthweight. The impact of this association was much stronger and more relevant in the group of women with respiratory allergies.

Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co-twin?

INTRODUCTION: The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury. MATERIAL AND METHODS: Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012-2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development. RESULTS: A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty-five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy-group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04-1.41, p = 0.014) and was higher in those surviving co-twins who developed anemia (OR 9.27, 95% CI: 1.50-57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68-11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome. CONCLUSIONS: Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co-twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.

Influence on operative time of immediate skin-to-skin care in low-risk primary cesarean births for breech presentation: Retrospective cohort study.

BACKGROUND: Multiple benefits for both, mother and baby have been reported from immediate skin-to-skin care (SSC). The aim of this study was to analyze the influence of SSC on operative time and blood loss in primary cesarean births for breech presentation. METHODS: A SSC protocol for cesarean birth was implemented in our institution on February 25, 2019. In this single-center retrospective cohort study, we compared the outcomes of planned primary cesarean births for breech presentation at term before and after its implementation. RESULTS: Data from 110 women who had a cesarean birth for breech presentation at term were analyzed, 55 in each group. Group 1 were women who had immediate SSC and Group 2 were women without immediate SSC. Maternal and surgical characteristics, and neonatal outcomes were similar in both groups. The mean operative time was 3.22 minutes shorter in the immediate SSC group compared with the not immediate SSC group (37.13 ± 12.27 vs 40.35 ± 12.23 minutes; P = 0.171). CONCLUSIONS: In conclusion, immediate SSC following a low-risk cesarean birth for breech presentation neither prolongs the operative time nor increases blood loss during the procedure. Although we were unable to demonstrate a significant reduction in the operative time with the immediate SSC protocol, a decrease of 3 minutes was noted.

Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia.

BACKGROUND: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat. RESULTS: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78-1.49]; P=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events. CONCLUSIONS: Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Registration: URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.

Quantitative proteomic analysis of serum-purified exosomes identifies putative pre-eclampsia-associated biomarkers.

BACKGROUND: The high incidence of pre-eclampsia, which affects 2-7% of all pregnancies, remains a major health concern. Detection of pre-eclampsia before the appearance of clinical symptoms is essential to allow early intervention, and would benefit from identification of plasma/serum biomarkers to help guide diagnosis and treatment. Liquid biopsy has emerged as a promising source of protein biomarkers that circumvents some of the inherent challenges of proteome-wide analysis of plasma/serum. In this respect, purified exosomes have the added benefit of being carriers of intercellular communication both in physiological and pathological conditions. METHODS: We compared the protein complement of purified exosomes from three different collections of control and pre-eclamptic serum samples, obtained at the end of the second trimester of pregnancy and at delivery. We employed shotgun label-free proteomics to investigate differential protein expression, which was then validated by targeted proteomics. RESULTS: We developed a purification method that yielded highly enriched exosome preparations. The presence of specific pregnancy protein markers suggested that a significant proportion of purified exosomes derived from tissues related to pregnancy. Quantitative proteomic analyses allowed us to identify 10, 114 and 98 differentially-regulated proteins in the three sample collections, with a high degree of concordance. Functional analysis suggested that these proteins participate in biological processes related to pre-eclampsia, including angiogenesis, inflammation and cell migration. The differential abundance of 66 proteins was validated by targeted proteomics. Finally, we studied the impact of the pre-eclampsia-associated exosomes in the proteome using an in vitro cellular model. CONCLUSIONS: We have identified and validated differential exosomal proteins in liquid biopsy of pregnant women that open new possibilities for early detection of pre-eclampsia. Additionally, the functional impact of the proteome composition of purified pre-eclamptic exosomes in target cells provides new information to better understand changes in embryo-maternal interactions and, consequently, the pathogenesis of this disease.

Longitudinal changes in fetal head biometry and fetoplacental circulation in fetuses with congenital heart defects.

INTRODUCTION: Objectives were to analyze changes in fetal cephalic biometry and fetoplacental circulation throughout pregnancy in fetuses with congenital heart defects. MATERIAL AND METHODS: Prospective study conducted on three university tertiary referral hospitals. Fetuses with the diagnosis of isolated congenital heart defects attending between 2014 and 2018 were included. Congenital heart defects were divided into two groups according to the oxygen supply to the central nervous system: group I (expected low placental blood content and low oxygen delivery to the brain) and group II (expected intermediate and high placental blood content). Fetal biometry and Doppler parameters were collected between 25-30 weeks of gestation and 34-40 weeks of gestation and transformed into Z scores. The results were compared with healthy controls. Finally, general linear modeling was performed to analyze repeated measurements. RESULTS: In all, 71 fetuses met the inclusion criteria. Fetuses with congenital heart defects had significantly smaller head (biparietal diameter [p < 0.001], head circumference [p = 0.001]) and abdominal circumference (p < 0.001), and lower estimated fetal weight (p < 0.001) than controls. When analyzing according to congenital heart defects type, head size was significantly smaller in group I compared with group II (p = 0.04). Regarding Doppler parameters, fetuses with congenital heart defects showed higher umbilical artery pulsatility index (p < 0.001) and lower cerebroplacental ratio (p = 0.044) than controls. In group I, umbilical artery pulsatility index was above the 95th centile in 15.4% of fetuses compared with 6.7% in group II and 1.9% in controls (p < 0.001); moreover, middle cerebral artery pulsatility index was below the 5th centile in 5.4% of group I fetuses compared with 0% in group II and 1.2% in controls (p = 0.011). General linear model for two measurements showed significant longitudinal changes in biometric parameters. Growth rate of fetal head through pregnancy (head circumference Z score) was lower in fetuses with congenital heart defects compared with controls (p = 0.043). In group I, the head circumference Z score longitudinal decrease was significantly higher than in group II (p < 0.001). CONCLUSIONS: Fetuses with congenital heart defects are at risk of smaller head size and Doppler changes. Growth rate of fetal head throughout pregnancy is also affected. These findings are mainly associated with cardiac defects with expected low oxygen supply to the central nervous system.

Gestational age-based reference ranges for cervical length and preterm birth prediction in triplet pregnancies: an observational retrospective study.

OBJECTIVES: To develop gestational age-based reference ranges for cervical length in triplet pregnancies. The secondary objective was to assess the performance of cervical length measured between 18 and 20 + 6 days for the prediction of preterm delivery before 28 and 32 weeks, respectively. METHODS: Observational retrospective study of triplet pregnancies in three Spanish tertiary-care hospitals between 2001 and 2019. Cervical length measurements were consecutively obtained between 15 and 34 weeks of gestation. Pregnancies undergoing multifetal reduction or fetal surgery were excluded. RESULTS: Two hundred and six triplet pregnancies were included in the final analysis. There was a quadratic decrease in cervical length with gestational age. The median and fifth centiles for cervical length at 20 weeks were 35 and 13 mm. In the prediction of preterm birth < 28 weeks, for a false positive rate of 5%, and 10%, the detection rates were 40.9%, and 40.9%, respectively, and the prediction of preterm birth < 32 weeks, 22.0% and 26.0%, respectively. CONCLUSIONS: In triplet pregnancies, cervical length decreases with gestational age. The performance of cervical length at 18-20 + 6 in screening for preterm birth before 28 and 32 weeks is poor.

Does the right ventricle experiment morphologic and functional changes similarly to the left ventricle during pregnancy?

OBJECTIVE: Morphological and functional right ventricular (RV) changes during normal pregnancy remain poorly characterized. Similar to left ventricle, RV load and function are expected to change, and establishing reference values for RV during a healthy pregnancy is critical for the evaluation of pregnancy-related heart disease. The aim of the study was to describe RV adaptation in a prospective cohort. METHODS: Serial echocardiographic examinations were performed in second trimester (24 ± 2 weeks), third (32 ± 2 week) trimester, and postpartum (>3 months after delivery). Nulliparous women were evaluated as control group. RV linear dimensions, areas, and function were assessed and compared. RESULTS: Forty-three pregnant women were evaluated and compared with nineteen nulliparous women as control. Function parameters decreased along gestation. RV fractional area fell from second to third trimester (52.01 ± 0.92 vs 48.73 ± 0.97, P < .05), as well as tricuspid annular plane systolic excursion (2.62 ± 0.05 vs 2.41 ± 0.05, P < .05); however, RV longitudinal strain (L) decreased earlier, showing main changes from second trimester (26.17 ± 0.86 vs 22.71 ± 0.57, P < .003, control vs second trimester). S'-wave velocity followed a different pattern without changes during pregnancy. RV diameters significantly increased during pregnancy: basal (3.65 ± 0.06 vs 3.90 ± 0.06, P < .05), mid- (2.70 ± 0.06 vs 3.00 ± 0.07, P < .05), longitudinal (6.90 ± 0.09 vs 7.32 ± 0.11, P < .05), and right ventricle outflow tract proximal diameter (3.20 ± 0.06 vs 3.44 ± 0.06, P < .05). RV areas also suffered early variation during pregnancy. In postpartum evaluation, all these changes were reversed. CONCLUSION: During pregnancy, RV experiments important variations. RV size increases, and its function decreases. Changes in LS were earlier compared with other function measures.

Expanding the indications for cell-free DNA in the maternal circulation: clinical considerations and implications.

Noninvasive prenatal testing for fetal aneuploidy using cell-free DNA has been widely integrated into routine obstetrical care. The scope of cell-free DNA testing has expanded from trisomies 21, 18, and 13 to include sex chromosome conditions, panels of specific microdeletions, and more recently genome-wide copy number variants and rare autosomal trisomies. Because the technical ability to test for a condition does not necessarily correspond with a clinical benefit to a population or to individual pregnant women, the benefits and harms of screening programs must be carefully weighed before implementation. Application of the World Health Organization criteria to cell-free DNA screening is informative when considering implementation of expanded cell-free DNA test menus. Most microdeletions and duplications are rare to the point that the prevalence has not even been defined and their natural history cannot be reliably predicted in the prenatal period. At the current time, scientific evidence regarding clinical performance of expanded cell-free DNA panels is lacking. Expanded cell-free DNA menus therefore create a dilemma for diagnosis, treatment, and counseling of patients. The clinical utility of expanding cell-free DNA testing to include panels of microdeletions and genome-wide assessment of large chromosomal imbalances has yet to be demonstrated; as such, the clinical implementation of this testing is premature.

Evaluation of Fetal Lung Maturity by Quantitative Analysis (quantusFLM) in Women with Gestational Diabetes Mellitus.

OBJECTIVES: The aim of the present study was to evaluate fetal lung maturity using the noninvasive method of quantitative ultrasound analysis of fetal lung texture (quantusFLM) in women with gestational diabetes mellitus (GDM). METHODS: A total of 96 women at 36-38 weeks of gestation were enrolled. They were classified as follows: 33 GDM cases treated with diet, 30 GDM cases treated with diet plus insulin, and 33 normoglycemic women (control group). A quantitative analysis of lung texture was performed. RESULTS: There were significant differences in the lung maturity results among groups (p = 0.004). These differences were established between the insulin-treated group of patients and both the control (p = 0.006) and diet-only (p = 0.003) groups. While none of the women in the control group or in the diet group had a high risk of immaturity, 16.7% of those treated with insulin (5/30) did (p = 0.003). There was no statistically significant correlation between HbA1c and the result of the test. CONCLUSIONS: Quantitative ultrasound study of fetal lung texture suggests that a significant percentage of pregnant women with GDM treated with insulin had fetal lung immaturity in the late preterm to early term.

Clinical and Economic Impact of Adopting Noninvasive Prenatal Testing as a Primary Screening Method for Fetal Aneuploidies in the General Pregnancy Population.

OBJECTIVE: To evaluate the clinical and economic impact of adopting noninvasive prenatal testing (NIPT) using circulating cell-free DNA as a first-line screening method for trisomy 21, 18, and 13 in the general pregnancy population. METHODS: A decision-analytical model was developed to assess the impact of adopting NIPT as a primary screening test compared to conventional screening methods. The model takes the Belgium perspective and includes only the direct medical cost of screening, diagnosis, and procedure-related complications. NIPT costs are EUR 260. Clinical outcomes and the cost per trisomy detected were assessed. Sensitivity analysis measured the impact of NIPT false-positive rate (FPR) on modelled results. RESULTS: The cost per trisomy detected was EUR 63,016 for conventional screening versus EUR 66,633 for NIPT, with a difference of EUR 3,617. NIPT reduced unnecessary invasive tests by 94.8%, decreased procedure-related miscarriages by 90.8%, and increased trisomies detected by 29.1%. Increasing the FPR of NIPT (from < 0.01 to 1.0%) increased the average number of invasive procedures required to diagnose a trisomy from 2.2 to 4.5, respectively. CONCLUSION: NIPT first-line screening at a reasonable cost is cost-effective and provides better clinical outcomes. However, modelled results are dependent on the adoption of an NIPT with a low FPR.

Optimal Gestational Weight Gain for Women with Gestational Diabetes and Morbid Obesity.

OBJECTIVES: Our aim was to investigate the greatest gestational weight gain (GWG) without adverse pregnancy complications in women with gestational diabetes mellitus (GDM) and morbid obesity. METHODS: An observational retrospective study including 3284 patients with single pregnancies and GDM was completed. Of the patients, 131 (4.0%) were classified as having pre-pregnancy morbid obesity (BMI ≥ 35 kg/m2). Perinatal complications were compared among BMI groups. In the group with morbid obesity, GWG threshold values to predict outcomes were examined based on sensitivity and specificity values under the receiver operating characteristic curve. RESULTS: GWG was higher in mothers with morbid obesity and macrosomic neonates: 11.3 (4.4-15.7) versus 4.8 (1.5-8.2) kg (p = 0.033). The GWG and neonatal ponderal index were positively correlated (r = 0.305, p = 0.001). The GWG was 7.0 (2.9-11.6) kg in women with hypertensive disorder versus 4.5 (1.0-7.5) kg in normotensive women (p = 0.017). A GWG above 5 kg was a risk factor for macrosomia (87.8% sensitivity, 54.7% specificity) and hypertensive disorder (70.0% sensitivity, 48.4% specificity). GWG associations were maintained after controlling for glycemic control, maternal and gestational age, parity, smoking and neonatal sex. CONCLUSIONS FOR PRACTICE: A GWG below 5 kg is recommended for women with GDM and morbid obesity. In these women, adequate GWG may prevent macrosomia, fetal overgrowth and hypertensive disorder.

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.

Monozygotic Monochorionic Twins Discordant for Trisomy 21: A Reason to Evaluate Both Fetuses: A Case Report.

BACKGROUND: The occurrence of a discordant chromosomal abnormality in monozygotic twins is an extremely rare condition. CASE: We report the prenatal sonographic findings and cytogenetic studies in a monochorionic twin pregnancy discordant for severe fetal anomalies. Amniocentesis was normal for both twins. The pregnancy was managed conservatively, resulting in the delivery of discordant twins at 28 weeks. Cytogenetic analysis performed on cultured lymphocytes from peripheral blood revealed a mosaic 47XY+21 (in 2% of the cells)/46XY (in 98%) in the structurally normal twin, and a mosaic 47XY+21 (4%)/46XY (96%) for the abnormal twin. The abnormal neonate died shortly after delivery. The structurally normal twin survived without sequelae and had a normal karyotype 2 years later. CONCLUSION: This report adds to the literature a case of a monochorionic twin pregnancy with a mosaic fetus who gives his co-twin trisomic cells through placental vascular anastomoses, this twin being a chimera, highlighting the necessity of performing molecular genetics with polymorphic DNA markers to differentiate chimerism from mosaicism and define the origin of cell lines.

Intrapartum ultrasound prior to Kristeller maneuver: an observational study.

OBJECTIVES: To evaluate the accuracy of criteria followed by obstetricians when performing a Kristeller maneuver in cases of prolonged second stage of labor. METHODS: In this prospective observational study, the station of the fetal head was measured using the angle of progression (intrapartum ultrasound) just prior to the intervention of the managing obstetrician in 52 women with prolonged second stage of labor. The managing obstetricians were blinded to the sonographic results. The decision of performing a Kristeller maneuver was taken by the obstetricians based on digital palpation and their experience. Delivery mode, Apgar score, umbilical artery pH value, episiotomy, perineal tears, bleeding, and time to delivery were recorded. RESULTS: Kristeller maneuver was performed in 36/52 (69.2%) cases. There were no significant differences between the Kristeller and the non-Kristeller group regarding the angle of progression. There were no significant differences between both groups with respect to delivery mode, perineal tears, episiotomy, bleeding, Apgar score, and umbilical artery pH value. CONCLUSIONS: Our study failed to define any criteria followed by obstetricians when performing a Kristeller maneuver in cases of prolonged second stage of labor. There was no relation between the angle of progression and the decision to perform a Kristeller maneuver.

Application of customized birth weight curves in the assessment of perinatal outcomes in infants of diabetic mothers.

OBJECTIVE: To determine whether the use of customized curves (CC) allows better detection of large- (LGA) or small-for-gestational age (SGA) infants at risk of adverse perinatal morbidity than non-CC in women with diabetes mellitus (DM). MATERIAL AND METHODS: A model of CC was applied to all infants of diabetic mothers (IDM) who attended the Hospital Universitario Materno Infantil de Canarias between 2008 and 2011. We compared perinatal outcomes of IDM classified as LGA or SGA by non-CC versus CC. RESULTS: One of 4 LGA was appropriate for gestational age (AGA) by CC (false-positive rate: 25%) and 30% of SGA by CC were not identified by non-CC (false-negative rate). False-positive LGA and SGA showed similar perinatal outcomes to AGA infants. The rates of cesarean section, cephalopelvic disproportion, total fetal distress and shoulder dystocia were significantly higher in false-negative LGA than in AGA by CC (p < 0.004, p < 0.02, p < 0.04 and p < 0.04, respectively). Fetal distress was higher in false-negative SGA than in AGA by CC (p < 0.03). DISCUSSION: In pregnancies complicated by DM, the use of CC allowed more accurate identification of LGA and SGA infants at high risk of perinatal morbidity than non-CC.