Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women.

BACKGROUND: Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS: We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS: We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS: The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Impact of Sonographer Experience, Insonation Angle, and Bladder Filling on Uterine Artery Doppler Measurements in the First Trimester of Pregnancy.

OBJECTIVE: To investigate the influence of different measurement conditions and ultrasound training level on uterine artery pulsatility index (UtA-PI) measurements as required for combined first trimester preeclampsia (PE) screening. METHODS: This was a prospective study of consecutive patients with singleton pregnancies presenting for an ultrasound examination between 11 and 14 weeks' gestation. UtA-PI measurements were conducted by residents in training and repeated by experienced sonographers thereafter. UtA-PI measurements were conducted under different examination conditions. First, the trainee sonographers performed transabdominal sagittal and transverse UtA-PI measurements without bladder filling. These measurements were then repeated by the expert sonographers. Additionally, the expert sonographers also performed transvaginal UtA-PI measurements and transabdominal measurements with bladder filling. Statistical analysis was conducted with the statistical software R and included descriptive statistics as well as 2-sided paired t tests. RESULTS: A total of 100 women were included in the study. Mean age was 31.7 ± 4.92 years and mean gestational week was 12.5 ± 0.53 weeks. A total of 56% were nulliparous and 44% were parous. UtA-PI was significantly lower if performed by a sonographer in training versus an experienced sonographer (P = .031). No significant difference was observed in comparing transverse and sagittal techniques (P = .241). There was also no significant difference in transabominal versus transvaginal measurements (P = .806) and with an empty versus full bladder (P = .444). CONCLUSION: Experience of sonographer has a significant impact on UtA-PI. Supervised onsite training is necessary to improve reliability and consistency of UtA-PI measurements and make PE screening reliable for implementation in a universal screening setting.

Effectiveness of first trimester maternal fat tissue measurement in prediction of gestational diabetes: a prospective cohort study.

Objective: The aim was to find a cost-effective, more practical method to be used in the early gestational weeks as an alternative to the oral glucose tolerance test (OGTT) for predicting gestational diabetes mellitus (GDM). The method selected was adipose tissue measurements made in the first trimester. Material and Methods: The study was designed as a prospective, cohort study. Ultrasound images were used to calculate abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) thicknesses of the first trimester pregnant women. Two groups were formed: those who were diagnosed with GDM and those who were not, based on the results of the OGTT performed in the same patients at 24th-28th weeks of gestation. Ultrasonographic records were examined and compared between these two groups using received operator characteristic curves and logistic regression analyses. Results: A total of 292 pregnant women were included, of whom 21.2% were diagnosed with GDM. In the group diagnosed with GDM, SAT, VAT and total adipose tissue (TAT) values were significantly higher than the women who did not have GDM. Threshold values for SAT, VAT and TAT were 18 mm, 55 mm and 55 mm. Conclusion: First trimester SAT, VAT and TAT measurements of pregnant women with GDM were significantly higher than those without GDM diagnosis. Although our results showed that adipose measurements cannot be an alternative to OGTT; they may be a powerful aid in identify at-risk pregnant women, suggesting early OGTT in the first trimester.

Correlation Between the First Trimester Two-Hour Postprandial Blood Glucose Greater Than 110 mg/dL for the Prediction of Gestational Diabetes Mellitus.

AIM: To determine the correlation between first-trimester two-hour postprandial blood glucose (PPBG) > 110 mg/dL for predicting gestational diabetes mellitus (GDM). METHODS: This prospective cohort study enrolled 200 women between 8 and 10 weeks of gestation from February 2022 to February 2024. All recruited pregnant women underwent testing for two-hour PPBS at 8-10 weeks and were followed up till delivery. GDM screening was done during 14-16, 24-28, and 32-34 weeks of gestation. RESULTS: Amongst women having PPBS > 110 mg/dL, 95.9% developed GDM, while in the group with PPBS < 110 mg/dL, only 4% developed GDM. In the PPBS > 110 mg/dL group, a significantly higher number of women were in the older age group (p < 0.049), had a higher BMI (p < 0.001), a family history of diabetes (p < 0.001), and previous history of abortion (p < 0.001). Women with PPBS > 110 mg/dL had significantly higher rates of cesarean section (p < 0.01), preterm delivery (p < 0.001), and macrosomia (p < 0.001). A positive correlation (r = 0.677; p < 0.001) was observed between first trimester two-hour PPBS and cord blood glucose levels. Similarly, a positive correlation (r = 0.465; p < 0.001) was present between insulin levels measured during the first trimester with cord blood insulin. The area under the curve (AUC) for PPBS was 0.969 (p < 0.001) with 95% CI: 0.933-0.988. PPBS > 110 mg/dL has a sensitivity of 95.9%, specificity of 95.6%, positive predictive value (PPV) of 95.9%, negative predictive value (NPV) of 95.7%, and diagnostic accuracy of 95.77% to predict GDM. CONCLUSION: PPBS > 110 mg/dL at two hours exhibits high levels of diagnostic accuracy for the prediction of GDM and is associated with adverse fetomaternal outcomes. PPBG is a superior, physiologic, and low-cost option compared to HbA1c for early prediction of GDM and can also be performed as a simple point-of-care test with a glucometer at home or in the periphery by healthcare workers (HCW) and in wellness centers.

First Trimester Fetal Clubfoot: A Novel Presentation of Severe Osteogenesis Imperfecta.

Talipes equinovarus, also called clubfoot, is a relatively common congenital defect affecting approximately one in every 1000 live births. Most cases of clubfoot are expected to be idiopathic and unrelated to an underlying genetic syndrome. In approximately 20% of cases, a clear genetic etiology is identified. Here we present two cases of bilateral clubfoot identified via fetal ultrasound in the first trimester associated with osteogenesis imperfecta diagnosed in the second trimester. Both fetuses presented with multiple fractures and were identified to have loss-of-function variants in COL1A1. An association between clubfeet in the first trimester and osteogenesis imperfecta has not been previously reported to the best of our knowledge, which leads to unique opportunities for prompt diagnosis, genetic counseling and testing, and appropriate management.

Study on ultrasound diagnosis and pathological anatomy of fetal complex congenital heart disease in the first trimester.

PURPOSE: To assess the feasibility of using the stereo-microscope to identify the pathological anatomy of the congenital heart diseases in the first trimester. METHODS: Fifteen fetuses of 8-12 weeks aborted due to prevent miscarriage failure and 42 fetuses of 11-14 weeks with congenital heart diseases were included in the study, we dissected their hearts through a stereo-microscope, then compared with the prenatal ultrasonographic diagnosis. RESULTS: Using stereomicroscopy, the positive view of the heart and the great arteries, the long axis view of the aortic arch, the inflow tract view of the bottom heart, the semilunar valve view of the bottom heart, and the transverse section of the ventricle were showed contented and obtained satisfactory images, but the structure of atrioventricular valve and venous system had a lower rate of display. CONCLUSION: The characteristic pathological changes of cardiac inflow and outflow tract can be obtained by dissecting the heart sequential under the stereo-microscopy. However it is often difficult to obtain satisfactory pathological sections for pulmonary venous abnormalities and Ebstein anomaly.

Prenatal and postnatal imaging for early detection of sirenomelia: A case study.

Sirenomelia is a rare congenital caudal abnormality. We applied two-dimensional, three-dimensional, and color Doppler ultrasound to diagnose a fetus with sirenomelia at 12 + 6 weeks. The fetus exhibited on ultrasound fused lower limbs, two tibiae in lower legs, no fibulae, knees in retroflexion, pelvic hypoplasia, hypoplasia of the lower lumbar vertebrae and coccyx, bilateral renal agenesis, no bladder, and a single umbilical artery. The postnatal X-ray revealed a fetus with two femurs, two tibiae, and no fibula. The results of chorionic villus aspiration indicated that the fetus was male with a normal karyotype (46, XY), and the microarray results were normal.

New insight on etiology: A chorionic bump with partial mole pregnancy case report from Syria.

This case report presents the association of a chorionic bump with a partial mole pregnancy in a 37-year-old G3P2 woman. The differential diagnosis of a partial mole was considered after transvaginal ultrasonography revealed a chorionic bump. Subsequent pathological analysis confirmed the diagnosis. While the etiology of the chorionic bump remains dubious, we hypothesize an alternative explanation for chorionic bump formation based on the presence of three unique pathological features: necrosis, edema, and hemorrhage.

First trimester maternal serum PAPP-A and free ß-hCG levels and risk of SGA or LGA in women with and without GDM.

BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were associated with SGA and LGA in GDM pregnancies and controls. METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fß-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fß-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fß-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA. CONCLUSION: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fß-hCG levels are associated with SGA only in non-GDM pregnancies.

Embryonic size and growth and adverse birth outcomes: the Rotterdam Periconception Cohort.

STUDY QUESTION: Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes? SUMMARY ANSWER: Larger embryonic crown-rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA). WHAT IS ALREADY KNOWN: Preterm birth, SGA, and congenital anomalies are the most prevalent adverse birth outcomes with lifelong health consequences as well as high medical and societal costs. In the late first and second trimesters of pregnancy, fetuses at risk for adverse birth outcomes can be identified using 2-dimensional ultrasonography (US). STUDY DESIGN, SIZE, DURATION: Between 2009 and 2018, singleton pregnancies were enrolled in this ongoing prospective Rotterdam Periconception Cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 918 pregnant women from a tertiary hospital in the Netherlands. Pregnancy dating was based on either a regular menstrual cycle (for natural pregnancies) or a conception date (for ART pregnancies). CRL and EV were measured using Virtual Reality software on 3-dimensional (3D) ultrasound scans, repeatedly performed around 7, 9, and 11 weeks of gestation. The main outcome measure was adverse birth outcome, defined as the composite of SGA (birth weight <10th percentile), preterm birth (<37th week of gestation), congenital anomalies (Eurocat criteria), stillbirth (>16th week of pregnancy), or early neonatal mortality (≤7 days of life). Reference curves for CRL and EV were constructed. Cross-sectional (CRL/EV <20th percentile at 7, 9, and 11 weeks of gestation) and longitudinal (CRL/EV growth trajectories between 6th and 13th weeks) regression analyses were performed, with adjustments for the participants' educational level, smoking, parity, age, BMI, geographical background, mode of conception, and fetal sex. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 918 pregnant women included, the median age was 32.3 years, and 404 (44%) pregnancies had been conceived via ART. In 199 (22%) pregnancies, there was an adverse birth outcome. Regression analyses showed that at 7 weeks of gestation onwards, embryos with a CRL <20th percentile had an ∼2-fold increased odds of adverse birth outcome (adjusted odds ratio (aOR) 2.03, 95% CI 1.21-3.39, P = 0.007). Similar associations were found for EV <20th percentile but were not statistically significant. These findings were mainly driven by the strong association between embryonic size and SGA (e.g. 7-week CRL: aOR 2.18 (1.16-4.09), P = 0.02; 9-week EV: aOR 2.09 (1.10-3.97, P = 0.02). Longitudinal growth trajectories of CRL, but not of EV, were associated with adverse birth outcomes. Both CRL and EV growth trajectories were associated with SGA. LIMITATIONS, REASONS FOR CAUTION: The tertiary hospital population and the availability of sophisticated 3D-ultrasound techniques limit the generalizability of this study to general populations and settings. WIDER IMPLICATIONS OF THE FINDINGS: Already very early in the first trimester of pregnancy, embryos with increased risks of an adverse birth outcome can be identified by using 3D-US and Virtual Reality. This expands the window of opportunity to enable the development of future interventions to potentially improve pregnancy outcomes and offspring health during their life-course. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: NL4115.

Telemedicine for the provision of medication abortion to pregnant people at up to twelve weeks of pregnancy: a systematic literature review and meta-analysis.

BACKGROUND: Telemedicine represents an important strategy to facilitate access to medication abortion (MAB) procedures, reduces distance barriers and expands coverage to underserved communities. The aim is evaluating the self-managed MAB (provided through telemedicine as the sole intervention or in comparison to in-person care) in pregnant people at up to 12 weeks of pregnancy. METHODS: A literature search was conducted using electronic databases: MEDLINE, Embase, Cochrane (Central Register of Controlled Trials and Database of Systematic Reviews), LILACS, SciELO, and Google Scholar. The search was based on the Population, Intervention, Comparison, Outcome, and Study Design (PICOS) framework, and was not restricted to any years of publication, and studies could be published in English or Spanish. Study screening and selection, risk of bias assessment, and data extraction were performed by peer reviewers. Risk of bias was evaluated with RoB 2.0 and ROBIS-I. A narrative and descriptive synthesis of the results was conducted. Meta-analyses with random-effects models were performed using Review Manager version 5.4 to calculate pooled risk differences, along with their individual 95% confidence intervals. The rate of evidence certainty was based on GRADE recommendations. RESULTS: 21 articles published between 2011 and 2022 met the inclusion criteria. Among them, 20 were observational studies, and 1 was a randomized clinical trial. Regarding the risk of bias, 5 studies had a serious risk, 15 had a moderate risk, and 1 had an undetermined risk. In terms of the type of intervention, 7 compared telemedicine to standard care. The meta-analysis of effectiveness revealed no statistically significant differences between the two modalities of care (RD = 0.01; 95%CI 0.00, 0.02). Our meta-analyses show that there were no significant differences in the occurrence of adverse events or in patient satisfaction when comparing the two methods of healthcare delivery. CONCLUSION: Telemedicine is an effective and viable alternative for MAB, similar to standard care. The occurrence of complications was low in both forms of healthcare delivery. Telemedicine services are an opportunity to expand access to safe abortion services.

First-trimester predictive models for adverse pregnancy outcomes-a base for implementation of strategies to prevent cardiovascular disease development.

Introduction: This study aimed to establish efficient, cost-effective, and early predictive models for adverse pregnancy outcomes based on the combinations of a minimum number of miRNA biomarkers, whose altered expression was observed in specific pregnancy-related complications and selected maternal clinical characteristics. Methods: This retrospective study included singleton pregnancies with gestational hypertension (GH, n = 83), preeclampsia (PE, n = 66), HELLP syndrome (n = 14), fetal growth restriction (FGR, n = 82), small for gestational age (SGA, n = 37), gestational diabetes mellitus (GDM, n = 121), preterm birth in the absence of other complications (n = 106), late miscarriage (n = 34), stillbirth (n = 24), and 80 normal term pregnancies. MiRNA gene expression profiling was performed on the whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: Most pregnancies with adverse outcomes were identified using the proposed approach (the combinations of selected miRNAs and appropriate maternal clinical characteristics) (GH, 69.88%; PE, 83.33%; HELLP, 92.86%; FGR, 73.17%; SGA, 81.08%; GDM on therapy, 89.47%; and late miscarriage, 84.85%). In the case of stillbirth, no addition of maternal clinical characteristics to the predictive model was necessary because a high detection rate was achieved by a combination of miRNA biomarkers only [91.67% cases at 10.0% false positive rate (FPR)]. Conclusion: The proposed models based on the combinations of selected cardiovascular disease-associated miRNAs and maternal clinical variables have a high predictive potential for identifying women at increased risk of adverse pregnancy outcomes; this can be incorporated into routine first-trimester screening programs. Preventive programs can be initiated based on these models to lower cardiovascular risk and prevent the development of metabolic/cardiovascular/cerebrovascular diseases because timely implementation of beneficial lifestyle strategies may reverse the dysregulation of miRNAs maintaining and controlling the cardiovascular system.

Placental Mosaicism for Autosomal Trisomies: Comprehensive Follow-up of 528 Danish Cases (1983-2021): Placental mosaicism for autosomal trisomies.

BACKGROUND: Mosaicism, characterized by the presence of two or more chromosomally distinct cell lines, is detected in 2-4% of chorionic villus samples. In these cases, the aberration may be confined to the placenta or additionally present in the fetus. Fetal involvement may manifest as fetal malformations, while confined placental mosaicism poses risks such as preterm birth and low birth weight. Differentiating between true fetal mosaicism and confined placental mosaicism at the time of the chorionic villus sampling is challenging and requires follow-up by an amniocentesis and ultrasonography. OBJECTIVES: To estimate the risk of fetal involvement or adverse pregnancy outcomes for specific chromosomes after detecting mosaicism for an autosomal trisomy in a chorionic villus sample and identify high (red), intermediate (yellow) and low (green) risk chromosomes. Further, to explore possible associations with level of mosaicism and screening parameters. STUDY DESIGN: A retrospective descriptive study of all singleton pregnancies with mosaicism detected in chorionic villus samples from 1983-2021 identified in the Danish Cytogenetic Central Registry and the Danish Fetal Medicine Database. RESULTS: Of 90,973 chorionic villus samples, 528 cases had mosaicism involving an autosomal trisomy and where genetic follow-up had been performed. The overall risk of fetal involvement was 13% (69/528) with extensive variations depending on which chromosome was involved (e.g., trisomy 7: 0% (0/55) or trisomy 21: 46% (19/41)). Higher levels of mosaicism in the chorionic villus sample suggested fetal involvement as mean mosaic level was 55% in true fetal mosaics vs 28% in cases confined to the placenta (p=0.0002). In cases with confined placental mosaicism (459/528), the risk of delivering small-for-gestational-age neonates was 14% (48/341). The risk of preterm birth (before 37 weeks) was 15% (51/343). The collective risk of adverse outcome was 22% (76/343) in pregnancies that continued and where information on birth weight and gestational age at birth was available. Adverse outcomes varied substantially between chromosomes. Also, multiple-of-the-median (MoM) values of pregnancy-associated plasma protein A was predictive of these issues as it was significantly lower in cases with adverse outcome compared to cases with a normal outcome (small for gestational age: 0.23 MoM vs 0.47 MoM, p<0.0001) or preterm birth: 0.25 MoM vs 0.47 MoM, p<0.0001). After the introduction of combined first trimester screening in 2004, the detection of cases with fetal involvement seemed to increase as the risk before 2004 was 9% (16/174) compared to 15% (53/354) after 2004 (risk ratio: 1.7 (95% CI: 1.0;2.8)). The risk of adverse outcome in confined placental mosaicism pregnancies increased from 16% (22/139) before 2004 to 27% (55/204) after 2004 (risk ratio 1.7 (95% CI: 1.1;2.7)) CONCLUSIONS: Introducing combined first trimester screening increased the detection of placental mosaicism with fetal involvement and confined placental mosaicism with adverse outcome. In cases of mosaicism in chorionic villus samples, the risk of fetal involvement and adverse outcomes varied considerably between chromosomes. Importantly, adverse outcomes were seen in confined placental mosaicism for many trisomies besides trisomy 16.

Fetal Echocardiography From 10 to 15 Weeks of Gestation - Reliability, Genetic Associations and Outcomes.

INTRODUCTION: There is increasing demand for accurate early fetal cardiac diagnosis (FCD). We assessed the accuracy of early fetal echo (EFE) conducted in our high volume fetal cardiac program and reviewed the spectrum of FCD, associated genetic anomalies and outcomes encountered. METHODS: We identified all EFE performed from 10+0-15+6 weeks of gestation from 2009-2021. We compared findings at EFE to fetal echo at ≥18+0 weeks or autopsy and documented genetic testing results for all FCD cases. For those with discrepancy between EFE and later exam, the discrepancy impact was reviewed. A score was used to quantify the anatomy assessed. RESULTS: 1662 EFE were performed in 1387 pregnancies; all but 41 were considered diagnostic. FCD was diagnosed at EFE in 130, including 101 major, 12 minor, 13 other FCD and 4 arrhythmias. In 14/130 with FCD EV imaging was undertaken which increased the score (1.6/9 vs 3.5/9 p=0.049). 35/130 had repeat EFE which increased the score (5.2/9 vs 7.4/9, p< 0.0001). Fetal loss occurred before confirmation of FCD in 16, termination in 64, and 11 were lost to follow up. Thirty-nine had autopsy and/or fetal echo ≥18+0: 35 had FCD confirmed and 4 had resolution. Of the 35 confirmed FCD, 27 had no, 7 minor and 1 major change. Of 1489 with normal EFE, later echo demonstrated FCD in 14: 3 major and 11 minor. In 16, FCD evolved including 4 arrhythmias and 12 with progressive FCD. Sensitivity, specificity, positive and negative predictive values of EFE in identifying major FCD were 92.9%, 100%, 100%, and 99.7%, respectively. In cases with FCD 85.4% had genetic testing, of whom 71% (60.8% of the total) had abnormal results. CONCLUSION: In our experience, EFE permits accurate diagnosis and exclusion of most FCD. EV imaging and repeat EFE studies improved the ability to visualise structures adequately.

Relationship between maternal serum uric acid in the first trimester and congenital heart diseases in offspring: A prospective cohort study.

Objective: This study aimed to investigate the relationship between maternal serum uric acid levels in the first trimester and the incidence of congenital heart diseases (CHDs) in offspring. Methods: This prospective cohort study was conducted in the southeast of China and involved 21,425 pregnant women and their offspring in the final analysis between 2019 and 2022. Fasting blood samples from pregnant women participating in the Fujian birth cohort study (11.3 ± 1.40 weeks of gestation) were analyzed for serum uric acid levels. The perinatal outcome was the incidence of CHDs. All fetuses with CHDs were confirmed by echocardiography doctors and pediatric cardiologists. Logistic regression analysis and restricted cubic spline (RCS) modeling were employed to investigate the relationship between serum uric acid level and the incidence of CHDs. Results: We observed that maternal log2-transformed values of serum uric acid were strongly associated with odds of CHDs in offspring (adjusted odds ratio [AOR] 1.589, 95 % CI [1.149, 2.198]). Compared to the lowest quartile, the AORs for maternal uric acid levels in the other quartiles and the corresponding risk of CHDs in offspring were 1.363 (95 % CI [1.036, 1.793]), 1.213 (95 % CI [0.914, 1.610]), and 1.472 (95 % CI [1.112, 1.949]), respectively. Hyperuricemia in the first trimester significantly increased the risk of CHDs in offspring 1.837 (95 % CI [1.073, 3.145]). Furthermore, RCS showed a linear relationship between maternal serum uric acid levels in the first trimester and the incidence of CHDs (P for nonlinearity = 0.71). Conclusions: The results of this study indicated that elevated maternal serum uric acid levels in the first trimester were associated with an increased incidence of CHDs in offspring.

Mono-(2-ethylhexyl) phthalate induces trophoblast hypoxia and mitochondrial dysfunction through HIF-1α-miR-210-3p axis in HTR-8/SVneo cell line.

The exposure to the ubiquitous phthalate metabolite mono-(2-ethylhexyl) phthalate (MEHP) is connected to dysregulated trophoblast function and placenta health; however, the underlying mechanisms preluding this scenario remain to be elucidated. In this study, we explored the hypoxemic effects of MEHP on a human placental first-trimester trophoblast cell line (HTR-8/Svneo). MEHP-treated trophoblast cells displayed significantly increased levels of oxidative stress and hypoxia-inducible factor-1 alpha (HIF-1α) attributed by the induction of hypoxia. Further, HIF-1α exhibited higher DNA binding activity and upregulated gene expression of its downstream target vascular endothelial growth factor A (VEGFA). The hypoxia-induced microRNA miR-210-3p was also significantly increased upon MEHP treatment followed by disrupted mitochondrial ATP generation and membrane potential. This was identified to possibly be facilitated by lowered mitochondrial DNA copy number and inhibited expression of electron transport chain subunits, such as mitochondrial complex-IV. These results suggest potential adverse effects of MEHP exposure in a trophoblast cell line mediated by HIF-1α and the epigenetic modulator miR-210-3p. Chronic placental hypoxia and oxidative stress have long been implicated in the pathogenesis of pregnancy complications such as preeclampsia. As we've revealed genetic and epigenetic factors underscoring a potential mechanism induced by MEHP, this brings to light another significant implication of phthalate exposure on maternal and fetal health.

Development of a spontaneous preterm birth predictive model using a panel of serum protein biomarkers for early pregnant women: A nested case-control study.

OBJECTIVE: To develop a model based on maternal serum liquid chromatography tandem mass spectrometry (LC-MS/MS) proteins to predict spontaneous preterm birth (sPTB). METHODS: This nested case-control study used the data from a cohort of 2053 women in China from July 1, 2018, to January 31, 2019. In total, 110 singleton pregnancies at 11-13+6 weeks of pregnancy were used for model development and internal validation. A total of 72 pregnancies at 20-32 weeks from an additional cohort of 2167 women were used to evaluate the scalability of the model. Maternal serum samples were analyzed by LC-MS/MS, and a predictive model was developed using machine learning algorithms. RESULTS: A novel predictive panel with four proteins, including soluble fms-like tyrosine kinase-1, matrix metalloproteinase 8, ceruloplasmin, and sex-hormone-binding globulin, was developed. The optimal model of logistic regression had an AUC of 0.934, with additional prediction of sPTB in second and third trimester (AUC = 0.868). CONCLUSION: First-trimester modeling based on maternal serum LC-MS/MS identifies pregnant women at risk of sPTB, which may provide utility in identifying women at risk at an early stage of pregnancy before clinical presentation to allow for earlier intervention.

Quantification of the size of subchorionic hematoma causing pregnancy-related complications: a retrospective cohort study.

PURPOSE: This study aimed to establish criteria for defining "large" subchorionic hematoma (SCH) and assess its association with pregnancy complications. METHOD: This was a retrospective cohort study conducted at our institution between 2019 and 2020. We compared the size of SCH between the pregnancy-related complication and non-complication groups, using two measurement methods. Receiver operating characteristic (ROC) curve analysis determined cutoff values. Additionally, we compared the occurrence of pregnancy complications among three groups: large SCH group (above the cutoff value), non-large SCH group (below the cutoff value), and non-SCH group. RESULTS: Of 1305 singleton pregnancies managed during the study, 80 cases were diagnosed with SCH. Pregnancy complications occurred in 15 patients. The patients with pregnancy complications had significantly larger SCH sizes with both measurement methods. For each method, the cutoff values calculated from the ROC curve analysis were as follows: Method 1, 25% (area under the ROC curve [AUC], 0.662); Method 2, 30% (AUC, 0.624). In Method 1, we found a significantly higher occurrence of preterm delivery in the large SCH group (24.1%) than in the non-large SCH (4.2%) and non-SCH groups (5.3%; all p < 0.01). In Method 2, there was a significantly higher occurrence of preterm delivery in the large SCH group (33.3%) than in the non-large SCH (6.5%) and non-SCH groups (5.3%; all p < 0.01). CONCLUSION: Large SCHs may indicate a high risk of pregnancy-related complications. Among these, recognizing and managing cases that exceed the aforementioned cutoff value as high-risk cases may be beneficial for reducing pregnancy complications.

Effect of treatment for early gestational diabetes mellitus on neonatal respiratory distress: A secondary analysis of the TOBOGM study.

OBJECTIVE: To identify factors associated with neonatal respiratory distress (NRD) in early Gestational diabetes mellitus (eGDM). DESIGN: Nested case-control analysis of the TOBOGM trial. SETTING: Seventeen hospitals: Australia, Sweden, Austria and India. POPULATION: Pregnant women, <20 weeks' gestation, singleton, GDM risk factors. METHODS: Women with GDM risk factors completed an oral glucose tolerance test (OGTT) before 20 weeks: those with eGDM (WHO-2013 criteria) were randomised to immediate or deferred GDM treatment. Logistic regression compared pregnancies with/without NRD, and in pregnancies with NRD, those with/without high-dependency nursery admission for ≤24 h with those admitted for >24 h. Comparisons were adjusted for age, pre-pregnancy body mass index, ethnicity, smoking, primigravity, education and site. Adjusted odds ratios (95% CI) are reported. MAIN OUTCOME MEASURES: NRD definition: ≥4 h of respiratory support (supplemental oxygen or supported ventilation) postpartum. Respiratory distress syndrome (RDS): Supported ventilation and ≥24 h nursery stay. RESULTS: Ninety-nine (12.5%) of 793 infants had NRD; incidence halved (0.50, 0.31-0.79) if GDM treatment was started early. NRD was associated with Caesarean section (2.31, 1.42-3.76), large for gestational age (LGA) (1.83, 1.09-3.08) and shorter gestation (0.95, 0.93-0.97 per day longer). Among NRD infants, >24 h nursery-stay was associated with higher OGTT 1-h glucose (1.38, 1.08-1.76 per mmol/L). Fifteen (2.0%) infants had RDS. CONCLUSIONS: Identifying and treating eGDM reduces NRD risk. NRD is more likely with Caesarean section, LGA and shorter gestation. Further studies are needed to understand the mechanisms behind this eGDM complication and any long-term effects.

Unveiling the human fetal-maternal interface during the first trimester: biophysical knowledge and gaps.

The intricate interplay between the developing placenta and fetal-maternal interactions is critical for pregnancy outcomes. Despite advancements, gaps persist in understanding biomechanics, transport processes, and blood circulation parameters, all of which are crucial for safe pregnancies. Moreover, the complexity of fetal-maternal interactions led to conflicting data and methodological variations. This review presents a comprehensive overview of current knowledge on fetal-maternal interface structures, with a particular focus on the first trimester. More in detail, the embryological development, structural characteristics, and physiological functions of placental chorionic plate and villi, fetal membranes and umbilical cord are discussed. Furthermore, a description of the main structures and features of maternal and fetal fluid dynamic exchanges is provided. However, ethical constraints and technological limitations pose still challenges to studying early placental development directly, which calls for sophisticated in vitro, microfluidic organotypic models for advancing our understanding. For this, knowledge about key in vivo parameters are necessary for their design. In this scenario, the integration of data from later gestational stages and mathematical/computational simulations have proven to be useful tools. Notwithstanding, further research into cellular and molecular mechanisms at the fetal-maternal interface is essential for enhancing prenatal care and improving maternal and fetal health outcomes.