Uncomplicated Term Pregnancies Research Articles

Identification of divergent placental profiles in clinically distinct pregnancy complications revealed by the transcriptome

IntroductionPregnancy complications, including preeclampsia (PE), preterm birth (PTB), and intra-uterine growth restriction (IUGR) have individually been associated with inflammation but the combined comparative analysis of their placental profiles at the transcriptomic and histological levels is lacking. MethodsBulk RNA-sequencing of human placental biopsies from uncomplicated term pregnancies (CTL) and pregnancies complicated with early-onset (EO), and late-onset (LO) PE, as well as PTB and term IUGR were used to characterize individual molecular profiles. We also applied immune-cell-specific cellular deconvolution to address local immune cell compositions and analyzed placental lesions by histology to further characterize these complications. ResultsTranscriptome analysis revealed that clinically distinct complications differentiated themselves in unique ways compared to CTLs. Only TMEM136 was commonly modulated. Compared to CTLs, we found that PTB and IUGR were the most distinct, with LOPE being the least distinct. PTB and IUGR revealed differently enhanced inflammatory pathways, where PTB had general inflammatory responses and IUGR had immune cell activation. This inflammation was reflected in the histological profile for PTB only, whereas structural lesions were elevated in all complications. Placental lesions additionally had corresponding enhancement in inflammatory and structural biological processes. We observed that having co-complications, particularly for PTB with or without IUGR, impacted placental transcriptomes. Lastly, cellular deconvolution uncovered shared immune features among the complications. DiscussionOverall, we provide evidence that these pregnancy complications are not only distinct in their clinical manifestations but also in their placental profiles, which could be leveraged to understand their underlying mechanisms and could offer therapeutic targets.

Correlation of fetal lung area with MRI derived pulmonary volume

BackgroundNeonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area. This study therefore aims to generate reference ranges for pulmonary volume and area in uncomplicated pregnancies, evaluate the correlation between prenatal pulmonary volume and area, as well as to assess the agreement between antenatal MRI-derived and neonatal CXR-derived pulmonary area in a cohort of fetuses that delivered shortly after the antenatal MRI investigation. MethodsFetal MRI datasets were retrospectively analysed from uncomplicated term pregnancies and a preterm cohort that delivered within 72 h of the fetal MRI. All examinations included T2 weighted single-shot turbo spin echo images in multiple planes. In-house pipelines were applied to correct for fetal motion using deformable slice-to-volume reconstruction. An MRI-derived lung area was manually segmented from the average intensity projection (AIP) images generated. Postnatal lung area in the preterm cohort was measured from neonatal CXRs within 24 h of delivery. Pearson correlation coefficient was used to correlate MRI-derived lung volume and area. A two-way absolute agreement was performed between the MRI-derived AIP lung area and CXR-derived lung area. ResultsDatasets from 180 controls and 10 preterm fetuses were suitable for analysis. Mean gestational age at MRI was 28.6 ± 4.2 weeks for controls and 28.7 ± 2.7 weeks for preterm neonates. MRI-derived lung area correlated strongly with lung volumes (p < 0.001). MRI-derived lung area had good agreement with the neonatal CXR-derived lung area in the preterm cohort [both lungs = 0.982]. ConclusionMRI-derived pulmonary area correlates well with absolute pulmonary volume and there is good correlation between MRI-derived pulmonary area and postnatal CXR-derived lung area when delivery occurs within a few days of the MRI examination. This may indicate that fetal MRI derived lung area may prove to be useful reference ranges for pulmonary areas derived from CXRs obtained in the perinatal period.

Predicting Time to Delivery in Hypertensive Disorders: Assessing PlGF and sFlt-1 with the Novel Parameter 'Mtp-Multiples of a Normal Term Placenta'.

Background: Imbalanced angiogenesis is characteristic of normal placental maturation but it also signals placental dysfunction, underlying hypertensive disorders during pregnancy. This study aimed to investigate the relationship between angiogenic placental aging, measured by markers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the new index "Multiples of a normal term placenta" (Mtp) and the duration of pregnancy. Methods: A retrospective observational study was conducted, including singleton pregnancies diagnosed or suspected of hypertensive disorders after the 20th gestational week. Mtp measures how far a single dosage of angiogenic marker deviates from the expected value in an uncomplicated full-term pregnancy (Mpt = sFlt-1/sFlt-1 reference value or PIGF/PIGF reference value). We considered the 90th, 95th, and 97.5th centiles for sFlt-1 and the 2.5th, 5th, and 10th centiles for PlGF as references. Results: The categories with longer time to delivery, regardless of gestational age, were: Mtp PlGF 10th c ≥ 2, ≥3 and Mtp sFlt-1 90th c ≤ 0.5 (median days of 9, 11, 15 days, respectively). These two categories Mtp sFlt-1 90th c ≥ 3 and Mtp sFlt-1 97.5th c ≥ 2 allow the identification of women at risk for imminent delivery within 1 day. Women who were deemed at low/medium risk based on the sFlt-1/PIGF ratio appeared to be at high risk when considering the individual values of sFlt-1 and/or PIGF. Conclusions: This new Mtp index for sFlt-1 and PlGF could be employed to assess the degree of placental aging in women with hypertensive disorders. It represents a valid tool for evaluating the risk of imminent birth, irrespective of gestational age, surpassing the current stratification based on the sFlt-1/PIGF ratio.

High-Dose Vitamin D Supplementation Significantly Affects the Placental Transcriptome.

Vitamin D deficiency is a highly prevalent obstetrical concern associated with an increased risk of complications like pre-eclampsia, gestational diabetes, and growth retardation. Vitamin D status in pregnancy is also linked to long-term offspring health, e.g., the risk of obesity, metabolic disease, and neurodevelopmental problems. Despite the suspected role of vitamin D in placental diseases and fetal development, there is limited knowledge on the effect of vitamin D on placental function. Thus, we performed next-generation RNA sequencing, comparing the placental transcriptome from uncomplicated term pregnancies receiving the often-recommended dose of 10 µg vitamin D/day (n = 36) with pregnancies receiving 90 µg/day (n = 34) from late first trimester to delivery. Maternal vitamin D status in the first trimester was also considered. We found that signaling pathways related to cell adhesion, immune function, and neurodevelopment were affected, supporting that increased vitamin D supplementation benefits placental function in established pregnancies without severe vitamin D deficiency, also underlining the importance of vitamin D in brain development. Specific effects of the first trimester vitamin D status and offspring sex were also identified. Further studies are warranted, addressing the optimal vitamin status during pregnancy with a focus on organ-specific vitamin D needs in individual pregnancies.

Placental accelerated aging in antenatal depression

Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging. This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery. The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009-2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental "epigenetic clock") that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment. There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (β=0.21 weeks [95% confidence interval, -0.17 to 0.58; P=.28] during the first trimester of pregnancy; β=0.41 weeks [95% confidence interval, 0.10-0.71; P=.009] during the second trimester of pregnancy; β=0.17 weeks [95% confidence interval, -0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29-1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (β=0.53 weeks; 95% confidence interval, 0.06-1.08; P=.03) but was not significant in pregnancies with female fetuses. Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction.

Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies.

A prospective observational study (ClinicalTrial ID: NCT05771415) was conducted to compare placental oxygenation in low-risk, uncomplicated term pregnancies measured by near-infrared spectroscopy (NIRS) in relation to the placental maturity grade determined by ultrasound assessment according to the Grannum scale. We included 34 pregnancies divided into two groups according to placental maturation. For each pregnancy, measurements were taken at the site above the central part of the placenta (test) and at the site outside of the placenta on the lower abdomen (control). Student's t-test was used to compare tissue oxygenation index (TOI) values among the study groups. The normality of distribution was proven by the Kolmogorov‒Smirnov test. In women with low placental maturity grade, the mean TOI value above the placenta was 70.38 ± 3.72, which was lower than the respective value in women with high placental maturity grade (77.99 ± 3.71; p < 0.001). The TOI values above the placenta and the control site were significantly different in both groups (70.38 ± 3.72 vs 67.83 ± 3.21 and 77.99 ± 3.71 vs 69.41 ± 3.93; p < 0.001). The results offer a new perspective on placental function based on specific non-invasive real-time oxygenation measurements. Unfortunately, and because of technical limitations, NIRS cannot yet be implemented as a routine clinical tool.

SFlt-1 Levels as a Predicting Tool in Placental Dysfunction Complications in Multiple Pregnancies.

several studies have demonstrated that angiogenic markers can improve the clinical management of hypertensive disorders (HDs) and fetal growth restriction (FGR) in singleton pregnancies, but few studies have evaluated the performance of these tests in multiple pregnancies. Our aim was to investigate the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in predicting adverse obstetric outcomes in hospitalized multiple pregnancies with HD (preeclampsia/gestational hypertension/uncontrolled chronic hypertension) and/or FGR in one or more fetuses. A retrospective analysis of multiple pregnancies with HD/FGR occurring after the 20th gestational week. Pregnant women were divided into two groups: women with high levels of sFlt-1 and those with low levels of sFlt-1. A value of sFlt-1 greater than or equal to 15,802 pg/mL was considered arbitrarily high, as it is equivalent to two times the 90th percentile expected in an uncomplicated full-term singleton pregnancy based on data from a prospective multicenter study (7901 pg/mL). The cohort included 39 multiple pregnancies. There were no cases of birth <34 weeks, HELLP syndrome, ICU admission, and urgent cesarean sections for HD/FGR complications reported among women with low levels of sFlt-1. A cut-off value of sFlt-1 ≥ 15,802 pg/mL could represent a valuable tool for predicting adverse obstetric outcomes in multiple pregnancies hospitalized for HD/FGR disorders, regardless of gestational age and chorionicity.

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit

BackgroundSerotonin (5-HT) is a biogenic monoamine with diverse functions in multiple human organs and tissues. During pregnancy, tightly regulated levels of 5-HT in the fetoplacental unit are critical for proper placental functions, fetal development, and programming. Despite being a non-neuronal organ, the placenta expresses a suite of homeostatic proteins, membrane transporters and metabolizing enzymes, to regulate monoamine levels. We hypothesized that placental 5-HT clearance is important for maintaining 5-HT levels in the fetoplacental unit. We therefore investigated placental 5-HT uptake from the umbilical circulation at physiological and supraphysiological levels as well as placental metabolism of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA efflux from trophoblast cells.MethodsWe employed a systematic approach using advanced organ-, tissue-, and cellular-level models of the human placenta to investigate the transport and metabolism of 5-HT in the fetoplacental unit. Human placentas from uncomplicated term pregnancies were used for perfusion studies, culturing explants, and isolating primary trophoblast cells.ResultsUsing the dually perfused placenta, we observed a high and concentration-dependent placental extraction of 5-HT from the fetal circulation. Subsequently, within the placenta, 5-HT was metabolized to 5-hydroxyindoleacetic acid (5-HIAA), which was then unidirectionally excreted to the maternal circulation. In the explant cultures and primary trophoblast cells, we show concentration- and inhibitor-dependent 5-HT uptake and metabolism and subsequent 5-HIAA release into the media. Droplet digital PCR revealed that the dominant gene in all models was MAO-A, supporting the crucial role of 5-HT metabolism in placental 5-HT clearance.ConclusionsTaken together, we present transcriptional and functional evidence that the human placenta has an efficient 5-HT clearance system involving (1) removal of 5-HT from the fetal circulation by OCT3, (2) metabolism to 5-HIAA by MAO-A, and (3) selective 5-HIAA excretion to the maternal circulation via the MRP2 transporter. This synchronized mechanism is critical for regulating 5-HT in the fetoplacental unit; however, it can be compromised by external insults such as antidepressant drugs.

Radiomics optimizing the evaluation of endometrial receptivity for women with unexplained recurrent pregnancy loss.

The optimization of endometrial receptivity (ER) through individualized therapies has been shown to enhance the likelihood of successful gestation. However, current practice lacks comprehensive methods for evaluating the ER of patients with recurrent pregnancy loss (RPL). Radiomics, an emerging AI-based technique that enables the extraction of mineable information from medical images, holds potential to offer a more objective and quantitative approach to ER assessment. This innovative tool may facilitate a deeper understanding of the endometrial environment and enable clinicians to optimize ER evaluation in RPL patients. This study aimed to identify ultrasound radiomics features associated with ER, with the purpose of predicting successful ongoing pregnancies in RPL patients, and to assess the predictive accuracy of these features against regular ER parameters. This retrospective, controlled study involved 262 patients with unexplained RPL and 273 controls with a history of uncomplicated full-term pregnancies. Radiomics features were extracted from ultrasound endometrial segmentation images to derive a radiomics score (rad-score) for each participant. Associations between rad-scores, baseline clinical variables, and sonographic data were evaluated using univariate and multivariate logistic regression analyses to identify potential indicators of RPL. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive accuracy of the rad-score and other identified indicators in discriminating RPL cases. Furthermore, the relationships between age and these identified indicators were assessed via Pearson correlation analysis. From the 1312 extracted radiomics features, five non-zero coefficient radiomics signatures were identified as significantly associated with RPL, forming the basis of the rad-score. Following multivariate logistic regression analysis, age, spiral artery pulsatility index (SA-PI), vascularisation index (VI), and rad-score emerged as independent correlates of RPL (all P<0.05). ROC curve analyses revealed the superior discriminative capability of the rad-score (AUC=0.882) over age (AUC=0.778), SA-PI (AUC=0.771), and VI (AUC=0.595). There were notable correlations between age and rad-score (r=0.275), VI (r=-0.224), and SA-PI (r=0.211), indicating age-related variations in RPL predictors. This study revealed a significant association between unexplained RPL and elevated endometrial rad-scores during the WOI. Furthermore, it demonstrated the potential of rad-scores as a promising predictive tool for successful ongoing pregnancies in RPL patients.

Risk of Cesarean Delivery after Vaginal Inserts with Prostaglandin Analogs and Single-Balloon Catheter Used for Cervical Ripening and Induction of Labor.

(1) Background: Induction of labor is currently the most frequently performed procedure in modern obstetrics, referring to more than one in five women, and it is postulated that the percentage of labor induction will increase. (2) Methods: In total, 2935 patients in uncomplicated full-term pregnancy fulfilled the study inclusion criteria and underwent induction of labor. Pregnant women were divided into three groups: IOL with Dinoprostone, Misoprostol vaginal suppositories, and Foley catheter. Outcomes, including cesarean section rates, time to delivery, and cesarean section indications, were analyzed. (3) Results: There was statistically significantly more cesarean sections within 24 h in the Misoprostol group in comparison with the Dinoprostone and Foley catheter groups (p < 0.0001). The percentage of patients who had a cesarean section due to clinically diagnosed threatened fetal asphyxia was 63% in the Dinoprostone group, 81.3% in the Misoprostol group, and 55.3% in the Foley catheter group. There were statistically significantly more cesarean deliveries due to nonreassuring fetal heart rate patterns within 24 h in the Misoprostol group in comparison with the Dinoprostone and Foley catheter groups (p = 0.0031 and p = 0.0363). (4) Conclusions: Misoprostol may cause a more turbulent and violent course of labor, with a higher rate of increased incidence of nonreassuring fetal heart rate patterns and cesarean deliveries. The use of a Dinoprostone vaginal insert or Foley catheter may provide longer labor, although still within 48 h, with a lower risk of cesarean section caused by nonreassuring fetal heart rate patterns.

Bioactive lipid mediators in plasma are predictors of preeclampsia irrespective of aspirin therapy

There are few early biomarkers to identify pregnancies at risk of preeclampsia (PE) and abnormal placental function. In this cross-sectional study, we utilized targeted ultra-performance liquid chromatography-ESI MS/MS and a linear regression model to identify specific bioactive lipids that serve as early predictors of PE. Plasma samples were collected from 57 pregnant women prior to 24-weeks of gestation with outcomes of either PE (n = 26) or uncomplicated term pregnancies (n = 31), and the profiles of eicosanoids and sphingolipids were evaluated. Significant differences were revealed in the eicosanoid, (±)11,12 DHET, as well as multiple classes of sphingolipids; ceramides, ceramide-1-phosphate, sphingomyelin, and monohexosylceramides; all of which were associated with the subsequent development of PE regardless of aspirin therapy. Profiles of these bioactive lipids were found to vary based on self-designated race. Additional analyses demonstrated that PE patients can be stratified based on the lipid profile as to PE with a preterm birth linked to significant differences in the levels of 12-HETE, 15-HETE, and resolvin D1. Furthermore, subjects referred to a high-risk OB/GYN clinic had higher levels of 20-HETE, arachidonic acid, and Resolvin D1 versus subjects recruited from a routine, general OB/GYN clinic. Overall, this study shows that quantitative changes in plasma bioactive lipids detected by ultra-performance liquid chromatography-ESI-MS/MS can serve as an early predictor of PE and stratify pregnant people for PE type and risk.

First Comparative Evaluation of Short-Chain Fatty Acids and Vitamin-K-Dependent Proteins Levels in Mother-Newborn Pairs at Birth.

The interplay between vitamin K (vitK) (as carboxylation cofactor, partially produced by the gut microbiota) and short-chain fatty acids (SCFAs), the end-product of fiber fermentation in the gut, has never been assessed in mother-newborn pairs, although newborns are considered vitK deficient and with sterile gut. We collected venous blood from 45 healthy mothers with uncomplicated term pregnancies and umbilical cord blood from their newborns at birth. The concentrations of total SCFAs and hepatic/extra-hepatic vitK-dependent proteins (VKDPs), as proxies of vitK status were assayed: undercarboxylated and total matrix Gla protein (ucMGP and tMGP), undercarboxylated osteocalcin (ucOC), undercarboxylated Gla-rich protein (ucGRP), and protein induced by vitK absence II (PIVKA-II). We found significantly higher ucOC (18.6-fold), ucMGP (9.2-fold), and PIVKA-II (5.6-fold) levels in newborns, while tMGP (5.1-fold) and SCFAs (2.4-fold) were higher in mothers, and ucGRP was insignificantly modified. In mother-newborn pairs, only ucGRP (r = 0.746, p < 0.01) and SCFAs (r = 0.428, p = 0.01) levels were correlated. Conclusions: We report for the first time the presence of SCFAs in humans at birth, probably transferred through the placenta to the fetus. The increased circulating undercarboxylated VKDPSs in newborns revealed a higher vitamin K deficiency at the extrahepatic level compared to liver VKDPs.

Deoxyribonucleic Acid, Ribonucleic Acid, and Protein in the Placentas of Normal and Selected Complicated Pregnancies

Placenta from uncomplicated term pregnancies resulting in the birth of male infants weighing between 2900 and 3800 grams were analyzed for deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein content. The mothers of the infants all had pre-pregnancy weights within +/- 15 percent expected body weight for body frame, according to the Metropolitan Life Tables. There were no significant differences, as regards the content of DNA, RNA and protein, between the placental cotyledons. Nine placenta from mothers giving birth to growth retarded infants were analyzed along with the placenta from six mothers with insulin dependent diabetes mellitus. A trend suggesting less DNA in the placenta of the severely growth retarded (symmetric) infants when compared with placenta from the normal pregnancies was not noted in the less severely growth retarded (asymmetric) infants. The placenta from the infants of diabetic pregnancies contained DNA and RNA in amounts similar to that found in normal pregnancy placenta but the protein content was greater.

Characteristics of Placental Histopathology in Women with Uncomplicated Pregnancies Affected by SARS-CoV-2 Infection at the Time of Delivery: A Single-Center Experience.

The aim of this study was, firstly, to analyze the histopathological characteristics of placentas in women with uneventful pregnancies and affected by COVID-19 at the time of delivery; and secondly, to correlate histological findings to maternal and neonatal characteristics. In our single-center prospective observational study, 46 placentas from term uncomplicated singleton pregnancies of patients with a documented SARS-CoV-2 infection at the time of delivery underwent histological examination. Despite a normal feto-maternal outcome, most of the placentas (82.6%) presented signs of maternal vascular malperfusion, while features of fetal vascular malperfusion were found in 54% of cases. No correlation was detected between maternal and neonatal characteristics and the severity of blood circulation disease, and abnormal findings were also described in asymptomatic patients. Moreover, we did not find any maternal symptoms or clinical details allowing for the prediction of abnormal placental findings in pregnancy complicated by COVID-19 infection. Our results suggest that SARS-CoV-2 infection during pregnancy could lead to acute placental dysfunction.

Global microRNA and protein expression in human term placenta.

Description of the global expression of microRNAs (miRNAs) and proteins in healthy human term placentas may increase our knowledge of molecular biological pathways that are important for normal fetal growth and development in term pregnancy. The aim of this study was to explore the global expression of miRNAs and proteins, and to point out functions of importance in healthy term placentas. Placental samples (n = 19) were identified in a local biobank. All samples were from uncomplicated term pregnancies with vaginal births and healthy, normal weight newborns. Next-generation sequencing and nano-scale liquid chromatographic tandem mass spectrometry were used to analyse miRNA and protein expression, respectively. A total of 895 mature miRNAs and 6,523 proteins were detected in the placentas, of which 123 miRNAs and 346 proteins were highly abundant. The miRNAs were in high degree mapped to chromosomes 19, 14, and X. Analysis of the highly abundant miRNAs and proteins showed several significantly predicted functions in common, including immune and inflammatory response, lipid metabolism and development of the nervous system. The predicted function inflammatory response may reflect normal vaginal delivery, while lipid metabolism and neurodevelopment may be important processes for the term fetus. The data presented in this study, with complete miRNA and protein findings, will enhance the knowledge base for future research in the field of placental function and pathology.

Uteroplacental versus fetal use of glucose in healthy pregnancies at term. A human in vivo study

IntroductionFetal glucose is thought to originate from maternal glucose driven across the placenta by a maternal-fetal glucose gradient. Still, there is no correlation between the mass of glucose taken up by the uteroplacenta and the fetal uptake. We propose a hypothesis that the uteroplacenta's own treatment of glucose affects the net mass of glucose taken up by the fetus, independent of the maternal-fetal gradient. MethodsWe performed a human in vivo study of term uncomplicated pregnancies including seventy healthy women delivered by scheduled cesarean delivery. We measured uterine and umbilical blood flow by Doppler ultrasonography, and glucose concentrations in the maternal radial artery, uterine vein, umbilical artery and vein. We calculated Spearman's correlations between uteroplacental and fetal glucose uptake within tertiles of placental glucose consumption. ResultsThere were significant correlations between uteroplacental uptake and fetal uptake of glucose when determined within each tertile (Spearman's rho 0.76, (p < 0.001); 0.94 (p < 0.001) and 0.49 (p = 0.029) from lowest to highest tertile, respectively). The median (Q1, Q3) uteroplacental glucose consumption in each tertile was −88.8 (−140.3, 56.7), 29.7 (9.2, 47.4) and 174.7 (87.8, 226.1) (μmol/min). The corresponding median (Q1, Q3) fetal glucose uptake was 152.9 (94.2, 162.7), 110.8 (54.7, 167.2) and 66.6 (8.5, 122.1) (μmol/min). DiscussionThe maternal fetal glucose gradients were similar in the tertiles of placental glucose consumption. Still, the net mass of glucose taken up by the fetus was markedly different between the tertiles. Placental treatment of glucose exhibited a large variation from apparent production to consumption.

Association between the cervical sliding sign and successful induction of labor in women with an unfavorable cervix: A prospective observational study

ObjectivesTo evaluate the role of the cervical sliding sign (CSS) in the prediction of the outcome of induction of labor (IOL). Study designTwo-center prospective observational cohort study involving a non-consecutive series of uncomplicated singleton term pregnancies, planned for IOL, with a fetus in cephalic presentation and unfavorable cervix as defined by a Bishop score ≤ 6. The Bishop score was evaluated by transvaginal digital examination and the cervical length and CSS by transvaginal ultrasound. The presence of CSS was defined as the sliding of the anterior cervical lip on the posterior one under gentle pressure of the transvaginal probe. The primary outcome of the study was successful vaginal delivery within 24 h. The secondary outcome was the induction-to-active-labor time. The interobserver agreement for the CSS was also evaluated. ResultsOver a period of 12 months, 179 women were included. The CSS was found in 86 (48.0 %) patients and was associated with an increased likelihood of vaginal delivery within 24 h (60/86 or 69.8 % vs 27/93 or 29.0 %, P < 0.001) and a shorter induction-to-active-labor time (954 ± 618 min vs 1416 ± 660 min, P < 0.001). Multivariable regression analysis showed that the CSS was an independent predictor of vaginal delivery within 24 h (aOR 5.37, 95 % CI 2.26–12.75) and shorter induction-to-active-labor time interval (HR 1.81, 95 % CI 1.19–2.74). The interobserver variability based on intraclass correlation coefficient for the CSS was excellent (ICC = 0.90). ConclusionIn women undergoing IOL with an unfavorable cervix, the CSS is associated with a higher frequency of vaginal delivery within 24 h and a shorter induction-to-active-labor time.

Accuracy of Fetal Biacromial Diameter and Derived Ultrasonographic Parameters to Predict Shoulder Dystocia: A Prospective Observational Study

Background and Objectives: Shoulder dystocia (ShD) is one of most dangerous obstetric complication. The objective of this study was to determine if the ultrasonographic fetal biacromial diameter (BA) and derived parameters could predict ShD in uncomplicated term pregnancies. Materials and Methods: We conducted a prospective observational study in a tertiary care university hospital from March 2021 to February 2022. We included all full-term pregnancies accepted for delivery that received an accurate ultrasonography (USG) scan before delivery. USG biometry and estimated fetal weight (EFW) were collected. Therefore, we evaluated the diameter of the mid-arm, the transverse thoracic diameter (TTD) and the biacromial diameter (BA). BA was estimated using Youssef’s formula: TTD + 2 mid-arm diameters. The primary outcome was the evaluation of BA and its related parameters (BA/biparietal diameter (BPD), BA/head circumference (HC) and BA–BPD in fetuses with ShD versus fetuses without ShD. Diagnostic accuracy for ShD of BA, BA/BPD, BA/HC and BA–BPD was evaluated using receiver operator curve (ROC) analysis. Results: 90 women were included in the analysis, four of these had ShD and required extra maneuvers after head delivery. BA was increased in fetuses with ShD (150.4 cm; 95% CI 133.2 cm to 167.6 cm) compared to no-ShD (133.5 cm; 95% CI 130.1 cm to 137.0 cm; p = 0.04). Significant differences were also found between ShD and no-ShD groups for BA/BPD (1.66 (95% CI 1.46 to 1.86) vs. 1.44 (95% CI 1.41 to 1.48); p = 0.04), BA/HC (0.45 (95% CI 0.40 to 0.49) vs. 0.39 (95% CI 0.38 to 0.40); p = 0.01), BA–BPD (60.0 mm (95% CI 42.4 to 77.6 cm) vs. 41.4 (95% CI 38.2 to 44.6); p = 0.03), respectively. ROC analysis showed an overall good accuracy for ShD, with an AUC of 0.821 (p = 0.001) for BA alone and 0.881 (p = 0.001), 0.857 (p = 0.016) and 0.867 (p = 0.013) for BA/BPD, BA–BPD and BA/HC, respectively. Conclusions: BA alone, as well as BA/BPD, BA/HC and BA–BPD might be useful predictors of ShD in uncomplicated term pregnancies. However, such evidence needs extensive confirmation by means of additional studies with large sample sizes, especially in case of pregnancies at high risk for ShD (i.e., gestational diabetes).

Comparison of Indoor vs Outdoor Induction of Labour in Full Term Uncomplicated Pregnancies.

Background: Induction of labour is an obstetric intervention when the continuation of pregnancy seems to be less beneficial than delivery. Cervical ripening increases the rate of success of labour and normal vaginal delivery. Outpatient cervical ripening is a striking option with benefits of increase maternal satisfaction, reduce hospital stay workload on health care resources Aim: To compare the fetomaternal outcome of indoor vs outdoor induction Methods: An observational cross sectional study was conducted in MCH PIMS, after taking approval from ethical review board from July 1, 2019 to December 31, 2019. A total of 412 women with singleton pregnancy of cephalic presentation and full term gestation were included. Group A was retained in emergency after induction (outdoor patient) while group B (indoor patient) induction was done in ward. All women followed till delivery and fetomaternal outcome i.e. cesarean section, apgar score &lt;7 at 5 minutes, meconium aspiration syndrome and NICU admission (yes/no) were noted. Results: In this study, caesarean section was recorded in 44(21.36%) patients with outdoor induction while in 67(32.52%) in women with indoor induction, Apgar score &lt;7 at 5 minutes was recorded in 4(1.94%) vs 15(7.28%) respectively, meconium aspiration syndrome in 6(2.91%) vs 35(16.99%) respectively and NICU admission in 3 (1.46%) versus 23(11.17%) respectively Conclusion: This study concluded that outdoor induction is better in terms of fetomaternal outcome as compared to indoor induction. Keywords: Induction of labour, outdoor, cesarean section.

Elective Induction of Labor or Expectant Management: Outcomes Among Nulliparous Women with Uncomplicated Pregnancies.

Cesarean birth rates among women who are nulliparous with uncomplicated full-term pregnancies have been shown to decrease if labor is electively induced. The purpose of this study was to compare the cesarean birth rate for women with pregnancies at 39.0 weeks' gestation or later admitted for spontaneous labor or medically indicated induction of labor (IOL) with that of women receiving elective IOL at term. A retrospective cohort study was conducted by searching electronic health records of all nulliparous women with uncomplicated pregnancies who gave birth between January 2018 through February 2020 at one academic medical center. Select maternal demographic data and approach to labor management were the primary variables analyzed in determining the odds of cesarean birth. A total of 1528 women were included in this study. Among these, 158 received elective IOL, and 1370 did not. The cesarean birth rates (31.0% vs 23.9%, elective induction of labor vs expectant management, respectively, P = .048), neonatal intensive care admissions (9.5% vs 7.6%, P = .41), and Apgar scores were similar among women in both management groups, respectively (P = .08). Accounting for other potential risk factors, the odds of having cesarean birth were not statistically different between management groups (adjusted odds ratio, 0.73; 95% CI, 0.5-1.1; P = .09). There were 2 fetal deaths among women whose labor was not electively induced. In the total cohort, women who were older, who had higher body mass index (BMI), and who identified as non-Hispanic Black had an increased odds of experiencing a cesarean birth. The associations between women in management groups and cesarean birth were not modified by age, BMI, race, or ethnicity (P = .33, .67, and .87, respectively). Elective IOL was not associated with lower cesarean rates in this study. Further research is needed before implementing clinical practice changes that encourage more use of IOL.