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OBJECTIVE:  The aim of Placental Assessment in Response to Environmental Pollution Study (PARENTs) was to determine whether imaging of the placenta by novel multiparametric magnetic resonance imaging (MRI) techniques in early pregnancy could help predict adverse pregnancy outcomes (APOs) due to ischemic placental disease (IPD). Additionally, we sought to determine maternal characteristics and environmental risk factors that contribute to IPD and secondary APOs. STUDY DESIGN:  Potential patients in their first trimester of pregnancy, who agreed to MRI of the placenta and measures of assessment of environmental pollution, were recruited into PARENTs, a prospective population-based cohort study. Participants were seen at three study visits during pregnancy and again at their delivery from 2015 to 2019. We collected data from interviews, chart abstractions, and imaging. Maternal biospecimens (serum, plasma, and urine) at antepartum study visits and delivery specimens (placenta, cord, and maternal blood) were collected, processed, and stored. The primary outcome was a composite of IPD, which included any of the following: placental abruption, hypertensive disease of pregnancy, fetal growth restriction, or a newborn of small for gestational age. RESULTS:  In this pilot cohort, of the 190 patients who completed pregnancy to viable delivery, 50 (26%) developed IPD. Among demographic characteristics, having a history of prior IPD in multiparous women was associated with the development of IPD. In the multiple novel perfusion measurements taken of the in vivo placenta using MRI, decreased high placental blood flow (mL/100 g/min) in early pregnancy (between 14 and 16 weeks) was found to be significantly associated with the later development of IPD. CONCLUSION:  Successful recruitment of the PARENTs prospective cohort demonstrated the feasibility and acceptability of the use of MRI in human pregnancy to study the placenta in vivo and at the same time collect environmental exposure data. Analysis is ongoing and we hope these methods will assist researchers in the design of prospective imaging studies of pregnancy. KEY POINTS: · MRI was acceptable and feasible for the study of the human placenta in vivo.. · Functional imaging of the placenta by MRI showed a significant decrease in high placental blood flow.. · Measures of environmental exposures are further being analyzed to predict IPD..

OBJECTIVE: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection. DESIGN AND SETTING: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021. PARTICIPANTS: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy. OUTCOME MEASURES: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies. RESULTS: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations. CONCLUSIONS: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period.

Although lipid metabolism in fetal livers under intrauterine growth restriction (IUGR) conditions has been widely studied, the implications of maternal undernutrition on fetal hepatic lipid metabolism, lipotoxic injury, and abnormal development remain largely unknown. Therefore, this study investigated the effects of maternal undernutrition on disordered hepatic lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses using transcriptome analysis. Seventeen singleton ewes were randomly divided into three groups on day 90 of pregnancy: a control group (CG; 0.63 MJ metabolic energy/body weight (ME/BW)0.75/day, n = 5), maternal undernutrition group 1 (MU1; 0.33 MJ ME/BW0.75/day, n = 6), and maternal undernutrition group 2 (MU2; 0.20 MJ ME/BW0.75/day, n = 6). The fetuses were euthanized and recovered on day 130 of pregnancy. The levels of free fatty acids (FFA) in maternal blood (P < 0.01), fetal blood (P < 0.01), and fetal livers (P < 0.05) were increased in the MU1 and MU2 groups, but fetal hepatic triglyceride (TG) levels in the MU2 group (P < 0.01) and β-hydroxybutyrate levels in the MU1 and MU2 groups (P < 0.01) were decreased compared to the CG. Severe inflammatory cell infiltration and increased non-alcoholic fatty liver disease activity scores were observed in MU1 and MU2 fetuses (P < 0.01). Progressive deposition of fetal hepatic reticular fibers and collagen fibers in the fetal livers of the MU1 and MU2 groups and significant hepatic fibrosis were observed in the MU2 fetuses (P < 0.05). Gene set enrichment analysis showed that genes involved in lipid accumulation and FFA beta oxidation were downregulated in both MU groups compared to those in the controls. The fetal liver mRNA expression of the β-oxidation regulator, acetyl-CoA acetyltransferase 1, and the TCA regulator, isocitrate dehydrogenase were reduced in MU1 (P < 0.05) and MU2 (P < 0.01) fetuses, and downregulated mRNA expression of long chain fatty acid CoA ligase 1 (P < 0.05) and glycerol-3-phosphate acyltransferase (P < 0.01) was observed in MU2 fetuses. Differentially expressed genes (DEGs) in MU1 versus CG (360 DEGs) and MU2 versus CG (746 DEGs) were identified using RNA sequencing. Bioinformatics analyses of the 231 intersecting DEGs between MU1 versus CG and MU2 versus CG indicated that neutrophil extracellular traps (NETs) were induced and played a central role in fetal hepatic injury in IUGR sheep. Increased maternal blood myeloperoxidase (MPO) levels (P < 0.01), NE (Elane)-positive areas in fetal liver sections (P < 0.05), and fetal liver MPO protein expression (P < 0.01) were found in the MU1 and MU2 groups; however, MPO levels were reduced in the fetal membrane (P < 0.01) and fetal blood (P < 0.05) in the MU1 group, and in the maternal-fetal placenta and fetal blood in the MU2 group (P < 0.01). Analysis of gene expression trends in the intersecting DEGs between MU1 versus CG (129 DEGs) and MU2 versus CG (515 DEGs) further revealed that 30 hub genes were essential regulators of the G2/M cell cycle, all of which were associated with hepatocellular carcinoma. G0/G1 phase cells of the fetal liver were reduced in the MU1 (P < 0.05) and MU2 (P < 0.01) groups, whereas G2/M phase cells were elevated in the MU1 and MU2 groups (P < 0.01). The representatives of upregulated hub genes and fetal liver protein expression of maternal embryonic leucine zipper kinase and protein regulator of cytokinesis 1 were progressively enhanced in the MU1 and MU2 groups (P < 0.01), and topoisomerase II alpha protein expression in the MU2 group (P < 0.05), as expected. These results indicate that FFA overload, severe lipotoxic injury, and NETs were induced, and disease-promoting regulators of the G2/M cell cycle were upregulated in the fetal liver of IUGR sheep. These findings provide new insights into the pathogenesis of impaired hepatic lipid metabolism and abnormal development and the molecular origin of post-natal liver disease in IUGR due to maternal undernutrition. This information can support the development of new therapeutic strategies. • FFA accumulated excessively and lipotoxic injury was induced in the IUGR sheep fetal livers. • NETs were triggered in the FFA-overloaded IUGR fetal livers, and play a central role in fetal hepatic injury. • Upregulated disease-promoting genes of G2/M cell cycle regulators in IUGR fetal liver worsen abnormal hepatic development. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design Setting Population Methods Main Outcome Measures Results Conclusions Trial Registration Uncertainty surrounds the risk–benefit of low‐molecular‐weight heparin to prevent postpartum venous thromboembolism (VTE). Data from randomised clinical trials (RCT) are critically needed, but recent feasibility studies in North America yielded low participation rates, with <1 enrolment per month per centre. Our aim was to assess the feasibility of a trial of postpartum short‐term enoxaparin in Europe.Pragmatic, open‐label pilot randomised controlled trial (RCT).Swiss tertiary hospital.Postpartum women, within 48 h of delivery, deemed at intermediate risk of VTE with at least one major risk factor (morbid obesity, thrombophilia, emergency caesarean section, pre‐eclampsia, preterm delivery, intrauterine growth restriction or systemic peripartum infection) and/or at least two minor risk factors.Participants were randomised to enoxaparin 40–60 mg once daily for 10 days or no treatment, with a 90‐day follow‐up.Participation rate and study acceptance (randomised participants among women in whom informed consent was sought).Recruitment was open for 25 weeks in 2022. Among 1504 postpartum women, 480 were eligible and 77 were randomised. The recruitment rate was 3.1 per week (13.3 per month) and the study acceptance was 23.8%. At 3 months, there was no VTE event, but one major, one nonmajor obstetrical bleeding and one surgical site complication, all in the enoxaparin group.This pilot RCT of postpartum thromboprophylaxis set in Switzerland yielded greater participation rate and acceptance than previous attempts in North America. It calls for a large, international, collaborative trial to guide this important clinical decision.ClinicalTrial.gov identifier: NCT05878899 and NCT04153760. [ABSTRACT FROM AUTHOR]

Background: The interplay between intrauterine and early postnatal environments has been associated with an increased risk of cardiovascular diseases in adulthood, including pulmonary arterial hypertension (PAH). While emerging evidence highlights the crucial role of mitochondrial pathology in PAH, the specific mechanisms driving fetal-originated PAH remain elusive. Methods and results: To elucidate the role of mitochondrial dynamics in the pathogenesis of fetal-originated PAH, we established a rat model of postnatal catch-up growth following intrauterine growth restriction (IUGR) to induce pulmonary arterial hypertension (PAH). RNA-seq analysis of pulmonary artery samples from the rats revealed dysregulated mitochondrial metabolic genes and pathways associated with increased pulmonary arterial pressure and pulmonary arterial remodeling in the RC group (postnatal catch-up growth following IUGR). In vitro experiments using pulmonary arterial smooth muscle cells (PASMCs) from the RC group demonstrated elevated proliferation, migration, and impaired mitochondrial functions. Notably, reduced expression of Mitofusion 2 (Mfn2), a mitochondrial outer membrane protein involved in mitochondrial fusion, was observed in the RC group. Reconstitution of Mfn2 resulted in enhanced mitochondrial fusion and improved mitochondrial functions in PASMCs of RC group, effectively reversing the Warburg effect. Importantly, Mfn2 reconstitution alleviated the PAH phenotype in the RC group rats. Conclusions: Imbalanced mitochondrial dynamics, characterized by reduced Mfn2 expression, plays a critical role in the development of fetal-originated PAH following postnatal catch-up growth after IUGR. Mfn2 emerges as a promising therapeutic strategy for managing IUGR-catch-up growth induced PAH. [ABSTRACT FROM AUTHOR]

Objective: To determine and compare pregnancy outcomes after bilateral uterine artery ligation (BUAL) or bilateral hypogastric artery ligation (BHAL) for postpartum hemorrhage (PPH). Material and Methods: This retrospective cross-sectional study was conducted from January 2010 to June 2018 at a tertiary referral hospital. Patients who had undergone arterial ligation for PPH were included in the study. Patients who had undergone BUAL and BHAL were compared with a control group in terms of fertility and pregnancy outcomes. Results: A total of 156 patients were included, of whom 47 underwent BUAl, 59 underwent BHAL and 50 were in the control group. There was no significant difference between the groups in subsequent pregnancies in terms of the incidence of miscarriage, fetal growth restriction, preeclampsia, primary cesarean deliveries, and infertility (p>0.05). There was a significant difference between all groups in gestational age at birth and birthweight. Preterm birth was observed in 32.2% of patients in the BHAL group, and this rate was significantly higher than in the BUAL (12.8%) and control (6%) groups (p=0.001). Conclusion: PPH is a life-threatening obstetric problem. The effects of interventions performed to reduce pelvic blood flow in patients may lead to persistent problems, such as preterm birth and low birth weight in the next pregnancy. However, these interventions do not appear to affect the risk of miscarriage. In subsequent pregnancies of patients who received BHAL, special attention should be paid to preterm birth. [ABSTRACT FROM AUTHOR]

Objectives: Small for gestational age (SGA) singletons are at increased risk for neurodevelopmental abnormalities. Scarce data exist regarding the long-term implications of SGA in twins. We opted to study the association between SGA of one twin and long-term neurologic related morbidity in dichorionic diamniotic twins. Study design: A population-based retrospective cohort study including consecutive dichorionic diamniotic twins, born between the years 1991 and 2021 at a tertiary medical center was conducted. Total and subtypes of neurologic related pediatric hospitalizations among SGA versus non-SGA twins were compared. A Kaplan–Meier survival curve was used to compare the cumulative neurologic morbidity incidence, and a Cox proportional hazards model was constructed to adjust for confounders. Results: The study population included 4222 newborns; 180 (4.3%) were SGA. Rate of long-term neurologic related hospitalizations was comparable between the two groups (8.7 vs. 8.0%, p = 0.755; Kaplan–Meier survival curve Log-rank p = 0.652). Using a Cox proportional hazards model, controlling for gender and birth order, no association was found between SGA and the risk for subsequent neurologic pediatric morbidity of the offspring (Adjusted HR = 1.0, 95% CI 0.6–1.8, p = 0.973). Conclusions: SGA is not associated with an increased risk for long-term pediatric neurologic morbidity in dichorionic diamniotic twins. [ABSTRACT FROM AUTHOR]

Purpose: While cell-free DNA (cfDNA) screening has emerged as a screening modality for common aneuploidies, further research and several publications over the past decade suggested some correlation between the low concentrations of cfDNA and a number of pregnancy-related complications. The primary goal of this systematic review and meta-analysis was to assess the potential value of low-ff levels in the prediction of subsequent PE/PIH, GDM, SGA/FGR, and PTB. The meta-analysis results aim at summarizing the currently available literature data and determining the clinical relevance of this biochemical marker and the potential necessity for additional investigation of its utility in complications other than the detection of common aneuploidies. Methods: This systematic review and meta-analysis was designed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. It included all observational studies that reported low -ff levels after the performance of non-invasive prenatal testing (NIPT) as part of the screening for chromosomal abnormalities and their association with adverse pregnancy outcomes, namely the subsequent development of hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and the detection of small for gestational age fetuses or growth-restricted fetuses. The Medline (1966–2041), Scopus (2004–2024), Clinicaltrials.gov (2008–2024), EMBASE (1980–2024), Cochrane Central Register of Controlled Trials CENTRAL (1999–2024) and Google Scholar (2004–2024) databases were used in our primary search along with the reference lists of electronically retrieved full-text papers. The date of our last search was set at February 29, 2024. Results: Our search identified 128 potentially relevant studies and,overall, 8 studies were included in the present systematic review that enrolled a total of 72,507 patients. Low ff of cfDNA cfDNA was positively associated with HDP (OR 1.66, 95% CI 1.34, 2.06, I-square test: 56%). Low ff of cfDNA was positively associated with GDM (OR 1.27, 95% CI 1.03, 1.56, I-square test: 76%). Furthermore, low ff levels were positively associated with SGA/FGR (OR 1.63, 95% CI 1.32, 2.03, I-square test: 0%). Low ff levels were positively correlated with the risk for PTB but the association did not manage to reach a statistical significant level (OR 1.22, 95% CI 0.89, 1.67, I-square test: 66%). Conclusion: Our study suggests that low ff is associated with increased risk of adverse perinatal outcomes, including PE/PIH, GDM, and SGA/FGR. However, the relationship between ff and PTB remains unclear due to conflicting evidence. It should be emphasized that further research is needed to reveal the underlying mechanisms behind the association of low ff with adverse pregnancy outcomes and explore its potential role in an overall prenatal screening, which could potentially not be limited to detecting aneuploidies. [ABSTRACT FROM AUTHOR]

Purpose: Fetal movements are crucial indicators of fetal well-being, with reduced fetal movements (RFM) suggesting potential fetal compromise. Fetal growth restriction (FGR), often linked to placental insufficiency, is a major cause of perinatal morbidity and mortality. This study aimed to investigate the neonatal, labor, and placental outcomes of FGR pregnancies with and without RFM at term. Methods: In this retrospective study, data from all term, singleton deliveries with FGR and concomitant RFM were obtained and compared to an equal control group of FGR without RFM. Maternal characteristics, pregnancy and neonatal outcomes, and placental histology were compared. The primary outcome was a composite of adverse neonatal outcomes. A multivariable regression analysis was performed to identify independent associations with adverse neonatal outcomes. Results: During the study period, 250 FGR neonates with concomitant RFM and an equal control group were identified. The groups did not differ in maternal demographics aside from significantly higher rates of maternal smoking in the RFM group (p < 0.001). Polyhydramnios and oligohydramnios (p = 0.032 and p = 0.007, respectively) and meconium-stained amniotic fluid (p < 0.001) were more prevalent in the FGR+RFM group. Additionally, the RFM group showed higher rates of adverse neonatal outcomes despite having larger neonates (p = 0.047 and p < 0.001, respectively). No significant differences were observed in placental findings. Logistic regression identified RFM as an independent predictor of adverse neonatal outcomes (aOR 2.45, 95% CI 1.27–4.73, p = 0.008). Conclusion: Reduced fetal movements are significant and independent predictors of worse neonatal outcomes in FGR pregnancies, suggesting an additional acute insult on top of underlying placental insufficiency. [ABSTRACT FROM AUTHOR]

Introduction: Microcephaly, characterized by abnormal head growth, can often serve as an initial indicator of congenital, genetic, or acquired disorders. In this study, we sought to evaluate the effectiveness of chromosomal microarray (CMA) testing in detecting abnormalities in both prenatal and postnatal cases of microcephaly. Materials and methods: CMA Testing: We conducted CMA testing on 87 prenatally-detected microcephaly cases and 742 postnatal cases at a single laboratory. We evaluated the CMA yield in relation to specific clinical characteristics. Results: In prenatal cases, pathogenic and likely pathogenic (LP) results were identified in 4.6% of cases, a significantly higher rate compared to low-risk pregnancies. The male-to-female ratio in this cohort was 3, and the CMA yield was not influenced by gender or other clinical parameters. For postnatal cases, the CMA yield was 15.0%, with a significantly higher detection rate associated with dysmorphism, hypotonia, epilepsy, congenital heart malformations (CHM), learning disabilities (LD), and a history of Fetal growth restriction (FGR). No specific recurrent copy number variations (CNVs) were observed, and the rate of variants of unknown significance was 3.9%. Conclusions: The yield of CMA testing in prenatal microcephaly is lower than in postnatal cases (4.6% vs. 15%). The presence of microcephaly, combined with dysmorphism, hypotonia, epilepsy, CHD, LD, and FGR, significantly increases the likelihood of an abnormal CMA result. [ABSTRACT FROM AUTHOR]

Purpose: Fetal cardiotocography is the most common method to assess fetal well-being during labor. Nevertheless, its predictive ability for acidemia is limited, both in low-risk and high-risk pregnancies (Nelson et al. in N Engl J Med 334: 613–9, 1996; Rinciples P et al. in Health and Human Development Workshop Report on Electronic Fetal Monitoring : Update on Definitions. no. 2007, 510–515, 2008), especially in high-risk pregnancies, such as those complicated by growth restriction. In this study we aim examine the association between deceleration and acceleration areas and other measure of fetal heart rate in intrapartum fetal monitoring and neonatal arterial cord blood pH in pregnancies complicated by growth restriction. Materials and methods: A retrospective cohort study of 100 deliveries complicated by growth restriction, delivered during 2018, was conducted. Known major fetal anomalies, non-vertex presentation and elective cesarean deliveries were excluded. Total deceleration and acceleration areas were calculated as the sum of the areas within the deceleration and acceleration, respectively. Results: In deliveries complicated by growth restriction, cord blood pH is significantly associated with total deceleration area (p = 0.05) and correlates with cumulative duration of the decelerations (Spearman's rank −0.363, p < 0.05), and total acceleration area (−0.358, p < 0.05). By comparing the cord blood pH in deliveries with a total deceleration area that was above and below the median total deceleration area, we demonstrated a significant difference between the categories. Conclusions: Cord blood pH significantly correlates with total deceleration area and other fetal monitoring characteristics in neonates with growth restriction. Future studies using real-time, machine-learning based techniques of fetal heart rate monitoring, may provide population specific threshold values that will support bedside clinical decision making and perhaps achieve better outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective of this prospective cohort study was to assess the usefulness of a predefined multidisciplinary care pathway-based management on pregnancy outcome(s) in women with SLE who already had at least one adverse obstetric outcome(s). Methods: Between March 2010 and March 2023, all consecutive, consenting women with SLE who already had at least one previous adverse obstetric outcome (preterm labour, pre-eclampsia, termination of pregnancy, miscarriage, intrauterine growth retardation (IUGR), preterm birth, low birth weight (LBW), intrauterine death (IUD) or stillbirth] were prospectively screened and counselled. The protocol comprised preconception and post-natal drug and disease status review, periodic ante-natal visits for the monitoring of pregnancy and drug and disease status review and post-natal drug and disease status review and contraception advice. Therapeutic changes were made as necessary at each visit. Results: A total of 213 women were screened and 197 women (age, 28 ± 6.34 years) were enrolled who had 226 pregnancies. Previous poor obstetric outcomes were miscarriage(s), 186; termination of pregnancy, 4; preterm labour, 51; IUGR, 36; IUD or stillbirth, 16; low birth weight (LBW), 44 and pre-eclampsia, 4. Seventy-seven (39%) women had secondary APS and 37 (19%) had a history of lupus nephritis. There were 194/226 (86%) live births [40 LBW (18%); caesarean section in 101 (45%)]. Thirty pregnancies culminated in miscarriages and 2 in IUDs (14%). Sixty-eight patients (30%) experienced lupus flare during pregnancy (36 mild, 20 moderate and 8 severe). Conclusion: Our experience underscores the usefulness of a predefined multidisciplinary care pathway-based management for improving pregnancy outcomes in women with SLE who had previous adverse outcomes. Key Points • In women with SLE who had previous adverse obstetric outcome(s) a risk of poor outcome in subsequent pregnancy remains. • Good pregnancy outcomes in these women could be achieved by predefined multidisciplinary care pathways focussed on addressing all relevant issues. • Improved access to rheumatology services and collaboration between rheumatologists and obstetricians is key to improving outcomes in SLE pregnancies. [ABSTRACT FROM AUTHOR]

Background: Thyroid dysfunction evaluation during pregnancy is important for the mother's health, obstetric outcomes, and the child's cognitive development. This study is conducted to know various thyroid disorders that can occur during antenatal and their impact on mother and fetus outcomes. Materials and Methods: This observational research was conducted over two years at a tertiary center in Western Rajasthan, India. Seven hundred and seventy-two low-risk singleton pregnant patients who met the inclusive criteria were recruited. The estimation of T3, T4, and TSH was done along with a routine investigation in antenatal women. Antenatal having abnormal thyroid profiles were then analyzed for mother and fetus problems. Results: The prevalence of thyroid dysfunction in antenatal women is 16.5%. Subclinical hypothyroidism (SCH) was seen in 12.5% of cases, overt hypothyroidism in 3.36%, and subclinical hyperthyroidism in only 0.51% of cases. Anti-TPO was positive in 46 (41.44%) women with hypothyroidism and 1 (25%) with hyperthyroidism. Compared to euthyroid women, women with overt hypothyroid (19.23% vs 3.1%, P = 0.002) and subclinical hypothyroid (9.27% vs 3.1%, P = 0.003) were found to be associated with a higher risk of hypertensive disease. Concerning fetal outcomes. There was a high risk for preterm (12.37% v/s 4.9%, P = 0.004) and fetal growth retardation (FGR) in patients with SCH (7.21% v/s 3.1%, P = 0.04). Conclusion: Considering the significant influence of thyroid disorders on mother and fetus outcomes, the screening for thyroid during pregnancy should be considered universally, particularly in developing countries with high prevalent rates, such as India. [ABSTRACT FROM AUTHOR]

Transfer RNA-derived small RNAs (tsRNAs), a recently identified subclass of small non-coding RNAs (sncRNAs), emerge through the cleavage of mature transfer RNA (tRNA) or tRNA precursors mediated by specific enzymes. The tumor necrosis factor (TNF) protein, a signaling molecule produced by activated macrophages, plays a pivotal role in systemic inflammation. Its multifaceted functions include the capacity to eliminate or hinder tumor cells, enhance the phagocytic capabilities of neutrophils, confer resistance against infections, induce fever, and prompt the production of acute phase proteins. Notably, four TNF-related tsRNAs have been conclusively linked to distinct diseases. Examples include 5′tiRNA-Gly in skeletal muscle injury, tsRNA-21109 in systemic lupus erythematosus (SLE), tRF-Leu-AAG-001 in endometriosis (EMs), and tsRNA-04002 in intervertebral disk degeneration (IDD). These tsRNAs exhibit the ability to suppress the expression of TNF-α. Additionally, KEGG analysis has identified seven tsRNAs potentially involved in modulating the TNF pathway, exerting their influence across a spectrum of non-cancerous diseases. Noteworthy instances include aberrant tiRNA-Ser-TGA-001 and tRF-Val-AAC-034 in intrauterine growth restriction (IUGR), irregular tRF-Ala-AGC-052 and tRF-Ala-TGC-027 in obesity, and deviant tiRNA-His-GTG-001, tRF-Ser-GCT-113, and tRF-Gln-TTG-035 in irritable bowel syndrome with diarrhea (IBS-D). This comprehensive review explores the biological functions and mechanisms of tsRNAs associated with the TNF signaling pathway in both cancer and other diseases, offering novel insights for future translational medical research. [ABSTRACT FROM AUTHOR]

Objective: To identify whether conventional methods of estimating fetal growth (Hadlock's formula), which relies heavily on abdominal circumference measurements, are accurate in fetuses with gastroschisis. Methods: A retrospective cohort study was performed between the period January 1, 2011 and December 31, 2021 in a tertiary referral maternity hospital identifying all pregnancies with a diagnosis of gastroschisis. Projected fetal weight was obtained using the formula (EFW [Hadlock's formula] + 185 g × [X/7]) where X was the number of days to delivery. Results: During the study period 41 cases were identified. The median maternal age was 25. The median BMI was 25 and 63% were primiparous women (n = 26). Median gestation at diagnosis was 21 weeks. Median gestation at delivery was 36 weeks. A total of 4.8% of mothers had a history of drug use (n = 2). The rate of maternal tobacco use was 21.9% (n = 9). A total of 4.8% of fetuses had additional congenital anomalies including amniotic band syndrome and myelomeningocele (n = 2). Estimated fetal weight (EFW) and birth weight data were available for 34 cases. A Wilcoxon signed‐rank test showed projected EFW using Hadlock's formula did not result in a statistically significant different birth weight (Z = −1.3, P = 0.169). Median projected weight and actual birth weight were 2241.35 and 2415 g respectively. Median difference was 0.64 g (95% CI: −148 to −28.5). Conclusion: Our data showed accuracy using standard formulae for EFW in fetuses with gastroschisis. Synopsis: Our study shows accuracy using standard formulae such as Hadlock's formula for estimating fetal weight in fetuses with abdominal wall defects such as gastroschisis. [ABSTRACT FROM AUTHOR]

Objectives: To develop a semi‐automated tool for measuring fetal abdominal wall thickness (AWT). To validate the software using images captured by other centers and create a nomogram for fetal AWT between 18 and 20 weeks. Methods: A semiautomated tool that measured AWT was developed using images captured at the routine 20‐week morphology scan. The software was developed using digital images captured routinely during scans of low‐risk women. Inter‐ and intraobserver reliability was assessed between manual and semi‐automated measures. The tool was validated using images acquired from other centers. Linear regression and quadratic polynomials were used to create a nomogram for AWT. Results: The semi‐automated tool was able to measure AWT in all images. Interoperator reliability was 0.90 and 0.97 (P < 0.05) for manual and semi‐automated methods, respectively. Measurement agreement varied between three operators from moderate to excellent (0.77, 0.87, 0.92), with overall agreement being good (0.85). The tool could be successfully applied to 89% of images from other centers. A nomogram was generated for AWT measurements of fetuses at 18–20 weeks in normal, low risk mothers. Conclusion: Semi‐automated measurement of AWT was feasible using images captured during the routine 20‐week scan. This approach had lower inter‐ and intraobserver variability compared to manual measurement. Synopsis: A semiautomated measurement of abdominal wall thickness (AWT) is being reported to measure fetal adiposity. This would have clinical application in gestational diabetes and fetal growth restriction. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to demonstrate the establishment of adrenal sparing in intrauterine growth restricted (IUGR) human fetuses. IUGR fetuses are a subgroup of small for gestational age (SGA) fetuses that are unable to reach their own growth potential because of chronic hypoxia and undernutrition. We hypothesized that in IUGR fetuses the adrenal gland is relatively larger and secretion of noradrenaline (NA), adrenaline (A), and cortisol is increased. Study Design: This is a prospective observational study including 65 singleton pregnancies (42 IUGR and 23 controls). Using two‐dimensional ultrasound, we measured fetal adrenal diameters and adrenal/abdominal circumference (AD/AC) ratio between 25 and 37 weeks. We considered only one measurement per fetus. In 21 pregnancies we also measured NA, A, and cortisol levels in arterial and venous fetal cord blood collected at the time of delivery. Results: The AD/AC ratio was significantly higher in IUGR fetuses than in controls. Cord NA and A levels were significantly higher in IUGR fetuses than in controls. An increase in cortisol secretion in IUGR fetuses was observed but the difference was not statistically significant. Conclusions: Adrenal sparing correlates with a relative increase in adrenal measurements and function. Synopsis: The adrenal gland of intrauterine growth‐restricted fetuses is relatively larger compared with controls and its function is enhanced. [ABSTRACT FROM AUTHOR]

Introduction: Women with systemic lupus erythematosus (SLE) have a higher risk for fetal and maternal complications. We aimed to investigate maternal and fetal complications in pregnant women with SLE compared to a high‐risk pregnancy cohort (HR) from a tertiary university center and a standard‐risk general population (SR) from the Austrian Birth Registry. Material and Methods: In this retrospective data analysis, we compared the incidence of fetal/neonatal and maternal complications of pregnancies and deliveries of women with SLE to age, body mass index and delivery date—matched high‐risk pregnancies from the same department, a progressive tertiary obstetric center and to a group of women, who represent pregnancies with standard obstetric risk from the Austrian Birth Registry. Results: One hundred women with SLE were compared to 300 women with high‐risk pregnancies and 207 039 women with standard‐risk pregnancies. The incidence of composite maternal complications (preeclampsia, Hemolysis, Elevated Liver enzymes and Low Platelets [HELLP] syndrome, pregnancy‐related hypertension, gestational diabetes mellitus, maternal death, thromboembolic events) was significantly higher in the SLE as compared to the SR group (28% vs. 6.28% SLE vs. SR, p = 0.001). There was no difference between the SLE and the HR groups (28% vs. 29.6% SLE vs. HR group, p = 0.80). The incidence of composite fetal complications (preterm birth before 37 weeks of gestation, stillbirths, birthweight less than 2500 g, fetal growth restriction, large for gestational age, admission to neonatal intensive care unit, 5‐min Apgar <7) was also higher in the SLE than in the SR group (55% vs. 25.54% SLE vs. SR p < 0.001) while the higher incidence of adverse fetal outcome was detected in the HR than in the SLE group (55% vs. 75% SLE vs. HR group, p = 0.0005). Conclusions: Although composite fetal risk is higher in the SLE group than in the general population, it is still significantly lower as compared to high‐risk pregnant women at a tertiary obstetric center. Prepregnancy counseling of women with SLE should put fetal and maternal risk in perspective, not only in relation to healthy, low risk cohorts, but also compared to mixed HR populations. [ABSTRACT FROM AUTHOR]

Cannabidivarin (CBDV) and cannabigerol (CBG) are minor phytocannabinoids from Cannabis sativa, whose health benefits have been reported. However, studies about the impact of these cannabinoids on fundamental cellular processes in placentation are scarce. Placental development involves physiological endoplasmic reticulum (ER) stress, however when exacerbated it can lead to altered angiogenesis and pregnancy disorders, such as intrauterine growth restriction and preeclampsia. In this work, the effects of CBDV and CBG (1–10 µM) on placental extravillous trophoblasts were studied, using the in vitro model HTR-8/SVneo cells. Both cannabinoids induced anti-proliferative effects and reactive oxygen/nitrogen species generation, which was dependent on transient receptor potential vanilloid 1 (TRPV1) activation. Moreover, CBDV and CBG significantly upregulated, in a TRPV-1 dependent manner, the gene expression of HSPA5/Glucose-regulated protein 78 (GRP78/BiP), a critical chaperone involved in ER stress and unfolded protein response (UPR) activation. Nevertheless, the UPR pathways were differentially activated. Both cannabinoids were able to recruit the IRE branch, while only CBDV enhanced the expression of downstream effectors of the PERK pathway, namely p-eIF2α, ATF4 and CHOP. It also augmented the activity of the apoptotic initiator caspases-8 and -9, though the effector caspases-3/-7 were not activated. TRB3 expression was increased by CBDV, which may hinder apoptosis termination. Moreover, both compounds upregulated the mRNA levels of the angiogenic factors VEGFA, PGF and sFLT1, and disrupted the endothelial-like behavior of HTR-8/SVneo cells, by reducing tube formation. Thus, CBDV and CBG treatment interferes with EVTs functions and may have a negative impact in placentation and in pregnancy outcome. [ABSTRACT FROM AUTHOR]

• Angiogenic biomarkers are important tools for the early prediction and diagnosis of preeclampsia. • Data from intervention trials do not support using angiogenic biomarkers for monitoring progressing of preeclampsia or deciding the timing of delivery. • There is insufficient evidence to recommend angiogenic biomarkers as an alternative to Doppler for surveillance and timing of delivery in fetal growth restriction. • Angiogenic biomarkers may have help differentiate between hypertension in chronic kidney disease from superimposed preeclampsia in pregnant women. Monitoring and timing of delivery in preterm preeclampsia and fetal growth restriction is one of the biggest challenges in Obstetrics. Finding the optimal time of delivery of these fetuses usually involves a trade-off between the severity of the disease and prematurity. So far, most clinical guidelines recommend the use of a combination between clinical, laboratory and ultrasound markers to guide the time of delivery. Angiogenic biomarkers, especially placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), have gained significant attention in recent years for their potential role in the prediction and diagnosis of placenta-related disorders including preeclampsia and fetal growth restriction. Another potential clinical application of the angiogenic biomarkers is for the differential diagnosis of patients with chronic kidney disease, as this condition shares similar clinical features with preeclampsia. Consequently, angiogenic biomarkers have been advocated as tools for monitoring and deciding the optimal time of the delivery of fetuses affected by placental dysfunction. In this clinical opinion, we critically review the available literature on PlGF and sFlt-1 for the surveillance and time of the delivery in fetuses affected by preterm preeclampsia and fetal growth restriction. Moreover, we explore the use of angiogenic biomarkers for the differentiation between chronic kidney disease and superimposed preeclampsia. [ABSTRACT FROM AUTHOR]

Prediction of fetal growth restriction (FGR) and small of gestational age (SGA) infants by using various ultrasound cardiac parameters in a logistic regression model. In this retrospective study we obtained standardized ultrasound images of 357 fetuses between the 20th and 39th week of gestation, 99 of these fetuses were between the 3rd and 10th growth percentile, 61 smaller than 3rd percentile and 197- appropriate for gestational age over the 10th percentile (control group). Several cardiac parameters were studied. The cardiothoracic ratio and sphericity of the ventricles was calculated. A binary logistic regression model was developed for prediction of growth restriction using the cardiac and biometric parameters. There were noticeable differences between the control and study group in the sphericity of the right ventricle (p = 0.000), left and right longitudinal ventricle length (pright = 0.000, pleft = 0.000), left ventricle transverse length (p = 0.000), heart diameter (p = 0.002), heart circumference (p = 0.000), heart area (p = 0.000), and thoracic diameter limited by the ribs (p = 0.002). There was no difference of the cardiothoracic ratio between groups. The logistic regression model achieved a prediction rate of 79.4 % with a sensitivity of 74.5 % and specificity of 83.2 %. The heart of growth restricted infants is characterized by a more globular right ventricle, shorter ventricle length and smaller thorax diameter. These parameters could improve prediction of FGR and SGA. [ABSTRACT FROM AUTHOR]

• MVFI can display the real-time perfusion status of fetal microvessels, including blood flow velocity, volume, and other related parameters. This technology is a non-invasive method that can be used to evaluate the blood flow situation in the fetal cranial region. • Growth restricted fetuses have lower biparietal diameter, head circumference, abdominal circumference, and femur length than normal fetuses, and their microvascular index and peak systolic velocity of internal arteries are also lower than normal fetuses. • The larger the microvascular index and peak systolic velocity of the internal artery, the more severe the fetal growth restriction. The study conducted retrospective analysis design, aiming to explore the use of Microvascular Imaging Technique (MVFI) to assess fetal cerebral microcirculation and analyze the relationship between Microvascular Index (MVI) and fetal growth and development. 100 pregnant women who met the criteria for fetal growth restriction (FGR) provided in the Expert Consensus on Fetal Growth Restriction (2019 Edition) and underwent routine prenatal examinations at the Obstetrics and Gynecology Department of Peking University Third Hospital from January 2021 to June 2023 were selected as the study subjects. A normal fetus with a fetal weight less than 10 % can be classified as FGR, Pregnant women with fetal umbilical artery (UA) systolic and diastolic (S/D) values ≥3 were included in the observation group, while 200 pregnant women with normal fetuses were selected as the control group during the same period. The fetuses' change in both groups were measured using color Doppler ultrasound, including bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The cerebral microcirculation of the fetuses in both groups was evaluated using MVFI, and the MVI values were compared. The clinical characteristics of FGR fetuses with umbilical artery S/D ratio ≥ 3 were summarized, and the correlation between fetal cerebral microvascular status and fetal growth and development was analyzed using Pearson correlation analysis. The outcomes told that the BPD, HC, AC, and FL values of the fetuses in the control group were lower the other's value (P < 0.05), and the MVI and peak systolic velocity of the middle cerebral artery (MCA-PSV) values were also lower in the control group (P < 0.05). Pearson correlation analysis revealed a positive correlation between fetal growth and development and MVI and MCA-PSV values in FGR fetuses. In conclusion, MVFI can monitor and quantitatively analyze fetal intracranial microcirculation, visualize slow blood flow in microvascular structures, and this study provides preliminary evidence of the close relationship between fetal cerebral microcirculation and intrauterine growth and development. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%. In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions: This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role. [ABSTRACT FROM AUTHOR]

Ultrasound‐based elastography techniques are increasingly available on modern ultrasound systems. The application of elastography extends the utility of ultrasound, yielding new information about the impact of disease on tissue biomechanics. By modifying the B‐mode imaging pulse, an Acoustic Radiation Force Impulse produces shear waves in selected tissue. Quantifying the speed of the resultant shear wave provides an indirect assessment of tissue stiffness, with stiffer tissue producing faster shear wave movement than softer tissue. Two main types of ultrasound shear wave elastography are currently in use. Point shear wave elastography uses one or two pulses to measure shear wave speeds over a small fixed area. Alternatively, two‐dimensional shear‐wave elastography provides a colour elastogram map over a larger area, allowing the operator to select specific regions of interest to measure shear wave speed. This article will discuss the essential physics principles, and clinical uses of two‐dimensional shear wave elastography, aiming to provide sonographers with a basic understanding of the technology and current applications. [ABSTRACT FROM AUTHOR]

We describe two cases of umbilical cord (UC) angiomyxoma diagnosed prenatally by sonography in the second trimester of pregnancy. In both cases, a complex mass was detected at the placental insertion site, characterized by an echoic nodule surrounding the umbilical vessels and distal edematous Wharton's jelly. Follow‐up scans showed that the mass grew mainly at the expense of its edematous component, with normal uteroplacental Dopplers throughout the remaining of the pregnancy. However, late‐onset fetal growth restriction complicated the progress of pregnancy, requiring delivery by Cesarean section at 37 weeks' gestation in both cases. Neonatal courses were unremarkable. An extensive review of the English literature was also performed, collecting 45 similar cases including ours. Our experience as well as the review of the literature confirms that UC angiomyxoma is an uncommon, sporadic condition that is usually detected incidentally during prenatal sonography and presents as an isolated finding. Nevertheless, it represents a high‐risk condition for pregnancy complications including prematurity, fetal growth restriction, and fetal demise. [ABSTRACT FROM AUTHOR]

BACKGROUND: The intestine is a barrier resisting various stress responses. Intrauterine growth restriction (IUGR) can cause damage to the intestinal barrier via destroying the balance of intestinal epithelial cells' proliferation and apoptosis. Bacillus subtilis has been reported to regulate intestinal epithelial cells' proliferation and apoptosis. Thus, the purpose of this study was to determine if B. subtilis could regulate intestinal epithelial cells' proliferation and apoptosis in intrauterine growth restriction suckling piglets. RESULTS: Compared with the normal birth weight group, the IUGR group showed greater mean optical density values of Ki‐67‐positive cells in the ileal crypt (P < 0.05). IUGR resulted in higher ability of proliferation and apoptosis of intestinal epithelial cells, by upregulation of the messenger RNA (mRNA) or proteins expression of leucine rich repeat containing G protein coupled receptor 5, Caspase‐3, Caspase‐7, β‐catenin, cyclinD1, B‐cell lymphoma‐2 associated agonist of cell death, and BCL2 associated X (P < 0.05), and downregulation of the mRNA or protein expression of B‐cell lymphoma‐2 and B‐cell lymphoma‐2‐like 1 (P < 0.05). However, B. subtilis supplementation decreased the mRNA or proteins expression of leucine rich repeat containing G protein coupled receptor 5, SPARC related modular calcium binding 2, tumor necrosis factor receptor superfamily member 19, cyclinD1, Caspase‐7, β‐catenin, B‐cell lymphoma‐2 associated agonist of cell death, and Caspase‐3 (P < 0.05), and increased the mRNA expression of B‐cell lymphoma‐2 (P < 0.05). CONCLUSION: IUGR led to excessive apoptosis of intestinal epithelial cells, which induced compensatory proliferation. However, B. subtilis treatment prevented intestinal epithelial cells of IUGR suckling piglets from excessive apoptosis. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Autosomal-recessive cutis laxa type 2 (ARCL2) is a rare genetic disorder caused by pyrroline-5-carboxylate reductase 1 (PYCR1) mutations and characterized by loose and sagging skin, typical facial features, intrauterine growth retardation, and developmental delay. To study the effect of PYCR1 mutations on protein function and clinical features, we identified a homozygous missense mutation c.559G > A (p.Ala187Thr) in PYCR1 in a Chinese child with typical clinical features, especially severe developmental delays. The three-dimensional (3D) model showed the modification of the hydrogen bonds produce a misfolding in the mutant PYCR1 protein. Mutagenesis and enzyme assay study revealed decreased activity of the mutant protein in vitro, indicating that this mutation impairs PYCR1 function. Our findings confirmed abnormal enzymatic activity and neurodevelopmental trajectory of this PYCR1 mutation. [ABSTRACT FROM AUTHOR]

This study aims to explore the link between dietary habits and adverse pregnancy outcomes (APOs), including preterm birth (PB), preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and spontaneous abortion (SA) through two‐sample Mendelian randomization (MR). We accessed publicly available genome‐wide association studies' (GWAS) summary statistics for dietary habits and APOs, respectively. We used five MR methods to synthesize MR estimates across genetic instruments. To ensure the robustness of our results, we assessed heterogeneity, and horizontal pleiotropy, and conducted sensitivity analyses. The primary analysis showed that intake of dried fruit (odds ratio (OR), 0.522; 95% confidence interval (CI): 0.291–0.935) and fresh fruit (OR, 0.487; 95% CI: 0.247–0.960) was related to a decreased risk of PB. While intake of tea (OR, 1.602; 95% CI: 1.069–2.403) and poultry (OR, 6.314; 95% CI: 1.266–31.488) was linked to a heightened risk of PB. Cheese intake was a protective factor against PE (OR, 0.557; 95% CI: 0.337–0.920) and GDM (OR, 0.391; 95% CI: 0.270–0.565). Intake of lamb/mutton had a negative relationship with PE (OR, 0.372; 95%CI: 0.145–0.954), whereas oily fish consumption showed a positive relationship with FGR (OR, 2.005; 95% CI: 1.205–3.339). However, after correction using the false discovery rate (FDR) analysis, only the intake of cheese showed a significant causal relationship with GDM (p < .001). Our study preliminarily found that cheese intake was significantly associated with the lower risk of GDM, while others were suggestively associated with the risk of APOs. Well‐designed prospective studies are still needed to confirm our findings in the future. [ABSTRACT FROM AUTHOR]