A spatially resolved timeline of the human maternal-fetal interface.

Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR)1-3. However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal-fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20 weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.

Spatial multiomics map of trophoblast development in early pregnancy.

The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels1. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia2. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal-fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids3,4 and trophoblast stem cells5. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell-cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy.

Maternal Smoking in the First Trimester and its Consequence on the Early Placenta.

Smoking during pregnancy increases the risk of adverse pregnancy outcomes, such as stillbirth and fetal growth restriction. This suggests impaired placental function and restricted nutrient and oxygen supply. Studies investigating placental tissue at the end of pregnancy have revealed increased DNA damage as a potential underlying cause, which is driven by various toxic smoke ingredients and oxidative stress induced by reactive oxygen species (ROS). However, in the first trimester, the placenta develops and differentiates, and many pregnancy pathologies associated with reduced placental function originate here. Therefore, we determined DNA damage in a cohort of first-trimester placental samples of verified smokers and nonsmokers. In fact, we observed an 80% increase in DNA breaks (P < .001) and shortened telomeres by 5.8% (P = .04) in placentas exposed to maternal smoking. Surprisingly, there was a decrease in ROS-mediated DNA damage, ie, 8-oxo-guanidine modifications, in placentas of the smoking group (-41%; P = .021), which paralleled the reduced expression of base excision DNA repair machinery, which restores oxidative DNA damage. Moreover, we observed that the increase in placental oxidant defense machinery expression, which usually occurs at the end of the first trimester in a healthy pregnancy as a result of the full onset of uteroplacental blood flow, was absent in the smoking group. Therefore, in early pregnancy, maternal smoking causes placental DNA damage, contributing to placental malfunction and increased risk of stillbirth and fetal growth restriction in pregnant women. Additionally, reduced ROS-mediated DNA damage along with no increase in antioxidant enzymes suggests a delay in the establishment of physiological uteroplacental blood flow at the end of the first trimester, which may further add to a disturbed placental development and function as a result of smoking in pregnancy.

The human placenta shapes the phenotype of decidual macrophages.

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (decPAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.

Shared risk factors for COVID-19 and preeclampsia in the first trimester: An observational study.

INTRODUCTION: The association between preeclampsia and coronavirus disease 2019 (COVID-19) is under study. Previous publications have hypothesized the existence of shared risk factors for both conditions or a deficient trophoblastic invasion as possible explanations for this association. The primary aim of this study was to examine baseline risk factors measured in the first-trimester combined screening for preeclampsia in pregnant women with COVID-19 compared with the general population. A secondary aim of this study was to compare risk factors among patients with mild and severe COVID-19. MATERIAL AND METHODS: This was an observational retrospective study conducted at Vall d'Hebron Hospital Campus (Catalonia, Spain). Study patients were 231 pregnant women undergoing the first-trimester screening for preeclampsia and positive for severe acute respiratory syndrome coronavirus 2 between February 2020 and September 2021. The reference cohort were 13 033 women of the general population from six centers across Catalonia from May 2019 to June 2021. Based on the need for hospitalization, patients were classified in two groups: mild and severe COVID-19. First-trimester screening for preeclampsia included maternal history, mean arterial blood pressure, mean uterine artery pulsatility index (UtAPI), placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A). RESULTS: The proportion of cases at high risk for preeclampsia was significantly higher among the COVID-19 group compared with the general population (19.0% and 13.2%, respectively; p = 0.012). When analyzing risk factors for preeclampsia individually, women with COVID-19 had higher median body mass index (25.2 vs 24.5, p = 0.041), higher UtAPI multiple of the median (MoM) (1.08 vs 1.00, p < 0.001), higher incidence of chronic hypertension (2.8% vs 0.9%, p = 0.015), and there were fewer smokers (5.7% vs 11.6%, p = 0.007). The MoMs of PlGF and PAPP-A did not differ significantly between both groups (0.96 vs 0.97, p = 0.760 and 1.00 vs 1.01, p = 0.432; respectively). CONCLUSIONS: In patients with COVID-19, there was a higher proportion of women at high risk for preeclampsia at the first-trimester screening than in the general population, mainly because of maternal risk factors, rather than placental signs of a deficient trophoblastic invasion.

Excessive gestational weight gain in early pregnancy and insufficient gestational weight gain in middle pregnancy increased risk of gestational diabetes mellitus.

BACKGROUND: Gestational weight gain (GWG) is associated with the risk of gestational diabetes mellitus (GDM). However, the effect of weight gain in different trimesters on the risk of GDM is unclear. This study aimed to evaluate the effect of GWG on GDM during different trimesters. METHODS: A birth cohort study was conducted from 2017 to 2020 in Shenzhen, China. In total, 51,205 participants were included comprising two models (early pregnancy model and middle pregnancy model). Gestational weight (kg) was measured at each prenatal clinical visit using a standardized weight scale. Logistic regression analysis was used to assess the risk of GDM. Interaction analysis and mediation effect analysis were performed in the middle pregnancy model. RESULTS: In the early pregnancy model, the risk of GDM was 0.858 times lower (95% confidence interval [CI]: 0.786, 0.937) with insufficient GWG (iGWG) and 1.201 times higher (95% CI: 1.097, 1.316) with excessive GWG after adjustment. In the middle pregnancy model, the risk of GDM associated with iGWG increased 1.595 times (95% CI: 1.418, 1.794) after adjustment; for excessive GWG, no significant difference was found ( P  = 0.223). Interaction analysis showed no interaction between GWG in early pregnancy (GWG-E) and GWG in middle pregnancy (GWG-M) ( F  = 1.268; P  = 0.280). The mediation effect analysis indicated that GWG-M plays a partial mediating role, with an effect proportion of 14.9%. CONCLUSIONS: eGWG-E and iGWG-M are associated with an increased risk of GDM. Strict control of weight gain in early pregnancy is needed, and sufficient nutrition should be provided in middle pregnancy.

Do empowered women receive better quality antenatal care in Pakistan? An analysis of demographic and health survey data.

INTRODUCTION: Quality antenatal care is a window of opportunity for improving maternal and neonatal outcomes. Numerous studies have shown a positive effect of women empowerment on improved coverage of maternal and reproductive health services, including antenatal care (ANC). However, there is scarce evidence on the association between women's empowerment and improved ANC services both in terms of coverage and quality. Addressing this gap, this paper examines the relationship between multi-dimensional measures of women empowerment on utilization of quality ANC (service coverage and consultation) in Pakistan. METHODS: We used Pakistan Demographic and Health Survey 2017-18 (PDHS) data which comprises of 6,602 currently married women aged between 15-49 years who had a live birth in the past five years preceding the survey. Our exposure variables were three-dimensional measures of women empowerment (social independence, decision making, and attitude towards domestic violence), and our outcome variables were quality of antenatal coverage [i.e. a composite binary measure based on skilled ANC (trained professional), timeliness (1st ANC visit during first trimester), sufficiency of ANC visits (4 or more)] and quality of ANC consultation (i.e. receiving at least 7 or more essential antenatal components out of 8). Data were analysed in Stata 16.0 software. Descriptive statistics were used to describe sample characteristics and binary logistic regression was employed to assess the association between empowerment and quality of antenatal care. RESULTS: We found that 41.4% of the women received quality ANC coverage and 30.6% received quality ANC consultations during pregnancy. After controlling for a number of socio-economic and demographic factors, all three measures of women's empowerment independently showed a positive relationship with both outcomes. Women with high autonomy (i.e. strongly opposed the notion of violence) in the domain of attitude to violence are 1.66 (95% CI 1.30-2.10) and 1.45 (95% CI 1.19-1.75) and times more likely to receive antenatal coverage and quality ANC consultations respectively, compared with women who ranked low on attitude to violence. Women who enjoy high social independence had 1.87 (95% CI 1.44-2.43) and 2.78 (95% CI 2.04-3.79) higher odds of quality antenatal coverage and consultations respectively, as compared with their counterparts. Similarly, women who had high autonomy in household decision making 1.98 (95% CI 1.60-2.44) and 1.56 (95% CI 2.17-1.91) were more likely to receive quality antenatal coverage and consultation respectively, as compared to women who possess low autonomy in household decision making. CONCLUSION: The quality of ANC coverage and consultation with service provider is considerably low in Pakistan. Women's empowerment related to social independence, gendered beliefs about violence, and decision-making have an independent positive association with the utilisation of quality antenatal care. Thus, efforts directed towards empowering women could be an effective strategy to improve utilisation of quality antenatal care in Pakistan.

Residential greenness and hair cortisol levels during the first trimester of pregnancy.

BACKGROUND AND AIM: Studies have shown that increased maternal cortisol level is associated with child adverse health outcomes. Hair cortisol (HC) is suitable for assessing long-term circulating cortisol concentration. Only two previous studies reported beneficial associations between cortisol and residential greenness during pregnancy and no study focused on the first trimester. Our aim was to evaluate the association between residential greenness and first trimester HC levels among pregnant women in Israel. METHODS: Women were recruited during second and third trimesters. Hair samples were collected from the scalp and retrospective HC levels during the first trimester were quantified for 217 women. HC levels were natural log transformed and outliers were excluded. Based on geocoded birth address, small area sociodemographic status (SES) and mean residential surrounding greenness were calculated using high-resolution satellite-based Normalised Difference Vegetation Index (NDVI) data at 100, 300 and 500-m buffers in a cross-sectional approach. In addition, longitudinal exposure to mean greenness during a week preconception and during the first trimester were calculated. Missing covariates were imputed and linearity of the associations were evaluated. Generalized linear models were used to estimate the crude and adjusted associations controlled for the relevant covariates. RESULTS: After exclusion of outliers, for 211 women, crude and adjusted beneficial associations between exposure to higher mean NDVI and HC levels were observed for all the exposure measures. An increase in 1 interquartile range of greenness (100 m buffer) was associated with a statistically significant lower estimated natural log mean HC level (-0.27 95% CI: -0.44; -0.11). The associations were robust to adjustment for covariates. The findings were consistent for different buffers, for the longitudinal approach, when all observations were included in the analysis and slightly stronger associations were observed for women with addresses geocoded at the home or street level. For most of the exposure measures, stronger associations were observed among those of lower sociodemographic status. CONCLUSION: Our findings that more greenness associated with reduced maternal cortisol levels measured in the hair during the first trimester, could have substantial implications for urban planners and public health professional. If our observations will be replicated, it may present a useful avenue for public-health intervention to promote health through the provision of greenness exposure during early pregnancy, specifically to disadvantage populations.

Mechanistic Target of Rapamycin Complex 1 Signaling Links Hypoxia to Increased IGFBP-1 Phosphorylation in Primary Human Decidualized Endometrial Stromal Cells.

Insulin-like growth factor-1 (IGF-1) bioavailability in pregnancy is governed by IGF binding protein (IGFBP-1) and its phosphorylation, which enhances the affinity of IGFBP-1 for the growth factor. The decidua is the predominant source of maternal IGFBP-1; however, the mechanisms regulating decidual IGFBP-1 secretion/phosphorylation are poorly understood. Using decidualized primary human endometrial stromal cells (HESCs) from first-trimester placenta, we tested the hypothesis that mTORC1 signaling mechanistically links hypoxia to decidual IGFBP-1 secretion/phosphorylation. Hypoxia inhibited mechanistic target of rapamycin (mTORC1) (p-P70-S6K/Thr389, -47%, p = 0.038; p-4E-BP1/Thr70, -55%, p = 0.012) and increased IGFBP-1 (total, +35%, p = 0.005; phosphorylated, Ser101/+82%, p = 0.018; Ser119/+88%, p = 0.039; Ser 169/+157%, p = 0.019). Targeted parallel reaction monitoring-mass spectrometry (PRM-MS) additionally demonstrated markedly increased dual IGFBP-1 phosphorylation (pSer98+Ser101; pSer169+Ser174) in hypoxia. IGFBP-1 hyperphosphorylation inhibited IGF-1 receptor autophosphorylation/ Tyr1135 (-29%, p = 0.002). Furthermore, silencing of tuberous sclerosis complex 2 (TSC2) activated mTORC1 (p-P70-S6K/Thr389, +68%, p = 0.038; p-4E-BP1/Thr70, +30%, p = 0.002) and reduced total/site-specific IGFBP-1 phosphorylation. Importantly, TSC2 siRNA prevented inhibition of mTORC1 and the increase in secretion/site-specific IGFBP-1 phosphorylation in hypoxia. PRM-MS indicated concomitant changes in protein kinase autophosphorylation (CK2/Tyr182; PKC/Thr497; PKC/Ser657). Overall, mTORC1 signaling mechanistically links hypoxia to IGFBP-1 secretion/phosphorylation in primary HESC, implicating decidual mTORC1 inhibition as a novel mechanism linking uteroplacental hypoxia to fetal growth restriction.

Low fetal fraction in obese women at first trimester cell-free DNA based prenatal screening is not accompanied by differences in total cell-free DNA.

OBJECTIVE: Reasons for first trimester noninvasive prenatal screening (NIPS) test failure in obese women remain elusive. As dilution from maternal sources may be explanatory, we determined the relationship between obesity, fetal fraction (FF), and total cell-free DNA (cfDNA) using our NIPS platform. METHODS: We assessed differences in first trimester (≤14 weeks) FF, indeterminate rate, and total cfDNA between obese (n = 518) and normal-weight women (n = 237) after exclusion of confounders (anticoagulation, autoimmunity, aneuploidy) and controlling for covariates. RESULTS: Fetal fraction was lower, and the indeterminate rate higher, in obese compared to controls (9.2% ± 4.4 vs. 12.5% ± 4.5, p < 0.001 and 8.4 vs. 1.7%, p < 0.001, respectively), but total cfDNA was not different (92.0 vs. 82.1 pg/µl, p = 0.10). For each week, the FF remained lower in obese women (all p < 0.01) but did not increase across the first trimester for either group. Obesity increased the likelihood of indeterminate result (OR 6.1, 95% CI 2.5, 14.8; p < 0.001) and maternal body mass index correlated with FF (ß -0.27, 95% CI -0.3, -0.22; p < 0.001), but not with total cfDNA (ß 0.49, 95% CI -0.55, 1.53; p = 0.3). CONCLUSIONS: First trimester obese women have persistently low FF and higher indeterminate rates, without differences in total cfDNA, suggesting placental-specific mechanisms versus dilution from maternal sources as a potential etiology.

A longitudinal analysis of arterial stiffness and wave reflection in preeclampsia: Identification of changepoints.

PURPOSE: Preeclampsia (PrE) is a leading complication of pregnancy characterized by vascular dysfunction. Characterizing the longitudinal changes in vascular function prior to PrE onset is critical to the identification of optimal timepoints for vascular assessment and the development of effective early screening strategies. METHODS: In this prospective longitudinal study of women with singleton high-risk pregnancies, arterial stiffness and wave reflection parameters were assessed using applanation tonometry at 10-13 weeks' gestation and repeated every 4 weeks throughout pregnancy. Changepoints in carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation index (AIx), time to wave reflection (T1R), pulse pressure amplification (PPA), and subendocardial viability ratio (SEVR) were compared between women who did and did not subsequently develop PrE. RESULTS: A changepoint in cfPWV and crPWV was detected at 14-17 weeks' gestation. cfPWV then increased in women who went on to develop PrE but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22-25 weeks' gestation. Conversely, crPWV converged in the two groups from a baseline difference of 1.05 m/s (95% credible interval: 0.37, 1.72). Women who subsequently developed PrE demonstrated an increase in AIx at 18-21 weeks' gestation that was not seen in women who did not develop PrE until 30-33 weeks. No differences in T1R, PPA, or SEVR were observed between the groups. CONCLUSIONS: Altered vascular adaptations were detected using measures of arterial stiffness and wave reflection in the early second trimester of pregnant women who developed PrE compared to those who did not. These findings demonstrate the potential clinical utility of arterial stiffness and wave reflection parameters as an early screening tool for PrE, which can be used to inform clinical management of high-risk pregnancies.

Exploring the mediating role of serum retinol-binding protein 4 in the relationship between sleep quality and insulin resistance in pregnant women.

AIMS: We aimed to explore the mediating role of plasma retinol-binding protein 4 (RBP4) in the relationship between sleep quality and insulin resistance (IR) among pregnant women. METHODS: We conducted a cross-sectional study including 263 pregnant women in the first trimester. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI). The ELISA and homeostasis model assessment (HOMA) was used to analyze plasma RBP4 and estimate IR. The mediating model was used to analyze the mediating role of RBP4 in the relationship between PSQI score and IR. RESULTS: In the multivariable linear regression model, the three terms were positively related with each other, PSQI score was positively associated with IR levels (ß = 0.55, p < 0.05). In the mediating model, RBP4 levels mediated completely the relationship between PSQI scores and IR levels (ß = 0.29, p < 0.0001). The indirect effect of RBP4 in the relation between sleep quality and IR explained 89.10% of total effect. CONCLUSIONS: RPB4 may play a complete mediating role in the relation between sleep quality and insulin resistance in early pregnancy. Improvements in sleep quality in the first trimester may provide a pathway to reduce plasma RBP4, which is beneficial for less IR and GDM prevention.

The effects of pre-pregnancy obesity and gestational weight gain on maternal lipid profiles, fatty acids and insulin resistance.

OBJECTIVES: Pregnancy is associated with physiological alterations in insulin sensitivity and lipid metabolism. This study investigates the associations between pregestational body mass index (pBMI) and the rate of gestational weight gain (rGWG) in the second trimester with the biomarkers of lipid, fatty acids metabolism and insulin resistance. METHODS: Sixty nine pregnant women followed. The body weights of the pregnant women were measured and blood samples were obtained at 11-14th and 24-28th weeks of pregnancy. Glucose, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, insulin levels and fatty acids were measured. Rate of GWG (kg/week) and The Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were calculated. The pregnant women were stratified according to their pBMI and the 2nd trimester rGWG. RESULTS: The rate of GWG was significantly higher for the group with pBMI<25, compared to the group with pBMI≥25 (p=0.024). Triglyceride, total cholesterol, LDL and HDL cholesterol were significantly increased in the second trimester compared with the first trimester. Palmitic acid, oleic acid, linoleic acid, myristic acid, docosahexaenoic acid (DHA), arachidonic acid (AA), total omega-6 (n - 6) and omega-3 (n - 3) fatty acid levels and n - 6/n - 3 ratio were significantly higher in the second trimester. Glucose was significantly decreased and insulin was increased in the second trimester. In the overweight/obese group; HOMA-IR, insulin, AA, palmitoleic acid and stearic acid were found to be high in comparison to the group with low/normal pBMI. No parameters were associated with rGWG. CONCLUSIONS: The changes in lipid parameters, free fatty acids, insulin and HOMA-IR in the second trimester were compatible with the changes in lipid metabolism and the development of insulin resistance. Pregestational BMI was shown to have a stronger influence on lipid profile, insulin resistance, and fatty acids than rGWG.

Prospective evaluation of first-trimester screening strategy for preterm pre-eclampsia and its clinical applicability in China.

OBJECTIVES: To evaluate, in a Chinese population, the performance of a screening strategy for preterm pre-eclampsia (PE) using The Fetal Medicine Foundation (FMF)'s competing-risks model and to explore its clinical applicability in mainland China. METHODS: This was a prospective, multicenter, observational cohort study including 10 899 women with singleton pregnancy who sought prenatal care at one of 13 hospitals, located in seven cities in mainland China, between 1 December 2017 and 30 December 2019. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and maternal serum levels of placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation were measured and converted into multiples of the median using Chinese reference ranges. Individualized risk for preterm PE was calculated using the FMF algorithm. Prior risk was calculated based on maternal demographic characteristics and obstetric history. We evaluated the efficiency of the screening strategy using various combinations of biomarkers and analyzed its predictive performance for a composite of placenta-associated adverse pregnancy outcomes, including PE, placental abruption, small-for-gestational age (SGA) and preterm birth, at fixed false-positive rates for preterm PE. RESULTS: We identified 312 pregnancies that developed PE, of which 117 cases were diagnosed as preterm PE (< 37 weeks' gestation). There were 386 pregnancies complicated by severe composite placenta-associated adverse outcome, including preterm PE, 146 cases of severe SGA (birth weight < 3rd percentile) neonate, 61 cases with placental abruption and 109 cases of early preterm birth < 34 gestational weeks. The triple-marker model containing biomarkers MAP, UtA-PI and PAPP-A achieved, at fixed false-positive rates of 10%, 15% and 20%, detection rates for preterm PE of 65.0%, 72.7% and 76.1%, respectively, and detection rates for severe composite placenta-associated adverse outcome of 34.7%, 41.7% and 46.4%, respectively. Replacing PAPP-A with PlGF or adding PlGF to the model did not improve the performance. Of women screening positive for preterm PE at a fixed 5% false-positive rate, an estimated 30% developed at least one placenta-associated adverse pregnancy outcome, including PE, placental abruption, SGA (birth weight < 10th percentile) and preterm birth < 37 weeks. CONCLUSIONS: The FMF competing-risks model for preterm PE was found to be effective in screening a mainland Chinese population. Women who screened positive for preterm PE had increased risk for other placenta-associated pregnancy complications. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Comparación de biomarcadores de primer trimestre en gestantes normotensas según su grado de obesidad en el tercer trimestre / Comparison of first trimester biomarkers in normotensive pregnancies according to their level of obesity in the third trimester

INTRODUCCIÓN: Nuestro trabajo tiene como objetivo aumentar la eficiencia del cribado de aneuploidías del primer trimestre de la gestación mediante la creación de modelos predictivos que sirvan para identificar gestantes en riesgo de desarrollar sobrepeso u obesidad en el tercer trimestre e instaurar medidas preventivas de obesidad a partir de ellos. MÉTODOS: Estudio observacional de tipo ambispectivo realizado en atención primaria, en el que se han recogido un total de 380 registros correspondientes a otros tantos embarazos. Se han muestreado 6 centros de salud con las variables siguientes: edad en la gestación, proteína A placentaria asociada al embarazo (PAPP-A) (mU/ml), gonadotropina coriónica humana (b-HCG) (ng/ml), semana de recogida de la muestra para el cribado de primer trimestre, índice de masa corporal (IMC) a las 12 y a las 28 semanas de gestación, TSH a las 12 semanas de gestación, presión arterial sistólica (PAS), presión arterial diastólica (PAD) y presión arterial media (PAM) a las 12 y a las 28 semanas de gestación. Se recodificó la variable IMC a las 28 semanas, clasificando a las embarazadas en peso normal (IMC<25), sobrepeso (IMC 25-29,99) y obesas (IMC≥30). El IMC a las 28 semanas recodificada fue la variable resultado del modelo de regresión logística ordinal. Utilizamos el estudio ANOVA de varios factores para discernir diferencias entre las presiones arteriales. Se aceptó un error alfa del 5%. RESULTADOS: Las medianas de la PAPP-A y de b-HCG medidas en el primer trimestre son menores de manera progresiva en los grupos de gestantes con normopeso, sobrepeso y obesidad observadas en el tercer trimestre. Estos valores son predictores del peso en el tercer trimestre (regresión logística ordinal) (PAPP-A: p = 0,022; b-HCG: p = 0,002). Ninguna gestante desarrolló preeclampsia. Las PAS, PAD y PAM en el tercer trimestre fueron significativamente diferentes (ANOVA de varios factores; p < 0,05). DISCUSIÓN: La regresión logística ordinal demuestra que la disminución de los valores observada de PAPP-A y de b-HCG en el primer trimestre es predictora del grado de obesidad de forma significativa y gradual en una muestra de gestantes normotensas. No hemos querido confeccionar un modelo de regresión ordinal incluyendo el IMC de las 12 semanas por la colinealidad interna que aportaría al estar basada la variable resultado en él. El efecto predictor de la b-HCG es más homogéneo que el de la PAPP-A para el estado de sobrepeso y obesidad

INTRODUCTION: This study aims to improve the efficiency of aneuploidy screening in the first trimester of pregnancy by creating predictive models that serve to identify pregnant women at risk of becoming overweight or obese in the third trimester and to using them to implement preventive measures of obesity. METHODS: An ambispective, observational, primary care study was conducted in which a total of 380 records corresponding to as many pregnancies were collected. Samples were collected from patients of 6 health centres, in order to determine the following variables: age at gestation, pregnancy-associated plasma protein A (PAPP-A) (mU/ml), human chorionic gonadotropin (b-HCG) (ng/ml), sample collection week for first trimester screening, body mass index at 12 and 28 weeks gestation (BMI), TSH at 12 weeks gestation, and systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MBP, respectively) at 12 and 28 weeks gestation. The BMI variable was recoded at 28 weeks, classifying pregnant women as normal weight (BMI<25), overweight (BMI 25-29.99), or obese (BMI≥30). The recoded BMI at 28 weeks was the variable resulting from the ordinal logistic regression model. An ANOVA study of several factors was used to discern differences between arterial pressures. A 5% alpha error was accepted. RESULTS: The PAPP-A and b-HCG medians measured in the first trimester are progressively lower in the groups of pregnant women with normal weight, overweight, and obesity observed in the third trimester. These values are predictors of the weight in the third trimester (ordinal logistic regression) (PAPP-A: P=.022; b-HCG: P=.002). No pregnant woman developed pre-eclampsia. The SBP, DBP, and MBP in the third trimester were significantly different (ANOVA in several factors; P<.05). DISCUSSION: The ordinal logistic regression demonstrates that the decrease in the observed values of PAPP-A and b-HCG in the first trimester is a predictor of the level of significant and gradual obesity in a sample of normotensive pregnant women. An ordinal regression model including the 12-week BMI was not made due to the internal collinearity that it would provide if the result variable was based on it. The predictive effect of b-HCG is more homogeneous than that of PAPP-A for the level of overweight and obesity

Taiwanese new direction in prediction of early pregnancy preeclampsia.

OBJECTIVE: First trimester screening is essential to preeclampsia (PE) prevention. Fetal Medicine Foundation (FMF) model combined maternal characteristics with mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI) and placental growth factor (PlGF) to estimate risk. High detection rate (DR) was observed in Asia. The study aims to evaluate performance of screening in Taiwan. MATERIALS AND METHODS: This was a prospective and non-interventional study between January, 2017 and June, 2018. Data was collected from 700 pregnant women at 11+0-13+6 gestational week. Maternal characteristics were recorded. MAP, UtAPI and PlGF were measured and converted into Multiple of the Median (MoM). Patient-specific risks were calculated with FMF model. Performance of screening was examined by ROC curve and DR. RESULTS: 25 women (3.57%) contracted PE, including 8 with preterm PE (1.14%). In preterm PE, mean MoM of MAP and UtAPI were higher (1.096 vs 1.000; 1.084 vs 1.035). Mean MoM of PlGF was lower (0.927 vs 1.031). DR in preterm PE achieved 12.5%, 50.0%, 50.0% and 62.5% at false-positive rate (FPR) of 5%, 10%, 15% and 20%. CONCLUSION: FMF model showed high DR for PE in Taiwan. Integration of PE and Down screening could set up a one-step workflow.

Aneuploidy in first trimester chorionic villi and spontaneous abortions: Windows into the origin and fate of aneuploidy through embryonic and fetal development.

OBJECTIVE: To review the mosaic autosomal trisomies in chorionic villi sample (CVS) trophoblasts, mesenchyme, and both cell lineages and to compare them with trisomies in spontaneous abortions. METHODS: Mosaic autosomal trisomies from 76 102 diagnostic CVS tests were classified as involving trophoblasts, involving mesenchyme, or present in both. Autosomal trisomies in products of conception were based on 18 published studies. We evaluated correlates between trisomy frequency with chromosome size or number of protein coding genes in the imbalance. RESULTS: Distinctly different patterns of trisomy were found in trophoblasts, mesenchyme, or both. In trisomic spontaneous abortions, there was a weak, borderline significant, inverse association between frequency and trisomic chromosome size and also with the number of protein coding genes involved (r = 0.43, P = 0.04 and r = 0.39, P = 0.07, respectively). These associations became stronger after excluding trisomy 16 (r = 0.52, P = 0.01 and r = 0.64, P = 0.001, respectively). Only CVS trisomies in both trophoblasts and mesenchyme resembled the trisomies found in spontaneous abortions and these were also associated with chromosome size and protein coding genes (r = 0.42, P = 0.05 and r = 0.57, P = 0.006, respectively). CONCLUSION: The abnormalities seen in CVS differ from those reported in early embryos. From conception through birth, there are lineage-specific, evolving spectrums of aneuploidy in trophoblasts, mesenchyme, and fetus.

Risk prediction model of gestational diabetes mellitus based on nomogram in a Chinese population cohort study.

To build a risk prediction model of gestational diabetes mellitus using nomogram to provide a simple-to-use clinical basis for the early prediction of gestational diabetes mellitus (GDM). This study is a prospective cohort study including 1385 pregnant women. (1) It is showed that the risk of GDM in women aged ≥ 35 years was 5.5 times higher than that in women aged < 25 years (95% CI: 1.27-23.73, p < 0.05). In the first trimester, the risk of GDM in women with abnormal triglyceride who were in their first trimester was 2.1 times higher than that of lipid normal women (95% CI: 1.12-3.91, p < 0.05). The area under the ROC curve of the nomogram of was 0.728 (95% CI: 0.683-0.772), the sensitivity and specificity of the model were 0.716 and 0.652, respectively. This study provides a simple and economic nomogram for the early prediction of GDM risk in the first trimester, and it has certain accuracy.