Umbilical Vascular Thromboembolism: High-Risk Factors, Diagnosis, Management, and Pregnancy Outcomes: A Scoping Review.

Umbilical vascular thromboembolism is a rare condition that can lead to serious consequences such as fetal hypoxia, fetal growth restriction, and even stillbirth. However, there is currently a lack of research on the pathology, pathogenesis, clinical management, and prognosis of this condition. Therefore, the purpose of this article is to analyze this condition's high-risk factors, clinical characteristics, pregnancy management, and discuss its corresponding pregnancy outcomes. Databases such as PubMed are searched using the relevant keywords of umbilical vascular thromboembolism in worldwide. And related information is analyzed such as maternal risk factors, fetal risk factors, umbilical cord and placental risk factors, and pregnancy outcomes. The literature search yields 113 articles, 64 of which meet the inclusion criteria for umbilical vascular thromboembolism. There are 4 retrospective cohort studies and 8 case series, the rest are all case reports. A total of 262 cases of umbilical vascular thromboembolism are found. The most common maternal complications and fetal related risk factors are diabetes (25 cases, 9.5%) and stillbirths (106 cases, 40.5%), respectively. Among these 262 cases, 98 (37.4%) cases are found by prenatal ultrasound to have umbilical vascular thromboembolism and the fetus is in a viable state with complete clinical information. In addition, considering the effectiveness and safety of low molecular weight heparin in thromboembolic conditions, twenty-four patients of umbilical artery thromboembolism attempted to use low molecular weight heparin during observation. Maternal diabetes was the highest risk factor for this condition. When umbilical artery thromboembolism occurs, the incidence of stillbirth increases. Premature patients with this condition can continue their pregnancy under close external monitoring. However, due to the small sample size, further research is needed.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction - A prospective study.

INTRODUCTION: The aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. METHODS: This was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. RESULTS: There were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). CONCLUSION: MVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Development and validation of prediction models for fetal growth restriction and birthweight: an individual participant data meta-analysis.

Background: Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes. Objectives: To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data. Design: Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis. Participants: Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies). Predictors: Maternal clinical characteristics, biochemical and ultrasound markers. Primary outcomes: fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks' gestation birthweight. Analysis: First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance (c-statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model. Results: Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c-statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g). Limitations: We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data. Future work: International Prediction of Pregnancy Complications models' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation. Conclusion: The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management. Study registration: This study is registered as PROSPERO CRD42019135045. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

One in ten babies is born small for their age. A third of such small babies are considered to be 'growth-restricted' as they have complications such as dying in the womb (stillbirth) or after birth (newborn death), cerebral palsy, or needing long stays in hospital. When growth restriction is suspected in fetuses, they are closely monitored and often delivered early to avoid complications. Hence, it is important that we identify growth-restricted babies early to plan care. Our goal was to provide personalised and accurate estimates of the mother's chances of having a growth-restricted baby and predict the baby's weight if delivered at various time points in pregnancy. To do so, first we tested how accurate existing risk calculators ('prediction models') were in predicting growth restriction and birthweight. We then developed new risk-calculators and studied their clinical and economic benefits. We did so by accessing the data from individual pregnant women and their babies in our large database library (International Prediction of Pregnancy Complications). Published risk-calculators had various definitions of growth restriction and none predicted the chances of having a growth-restricted baby using our definition. One predicted baby's birthweight. This risk-calculator performed well, but underpredicted the birthweight by up to 143 g. We developed two new risk-calculators to predict growth-restricted babies (International Prediction of Pregnancy Complications-fetal growth restriction) and birthweight (International Prediction of Pregnancy Complications-birthweight). Both calculators accurately predicted the chances of the baby being born with growth restriction, and its birthweight. The birthweight was underpredicted by <9.7 g. The calculators performed well in both mothers predicted to be low and high risk. Further research is needed to determine the impact of using these calculators in practice, and challenges to implementing them in practice. Both International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight risk calculators will inform healthcare professionals and empower parents make informed decisions on monitoring and timing of delivery.

The association between prenatal pyrethroids exposure and children's health - current research.

Exposure to pyrethroids, a widely used agricultural, forestry, and household insecticide, is a major public health concern due to its potential health effects on children. The aim of this review was to summarize the current knowledge of the effects of prenatal exposure to pyrethroids on the course and outcome of pregnancy, health status, and neurobehavioural development of children. A systematic and comprehensive search of the PubMed, Web of Science, and Scopus databases was conducted during January-February 2024. The review included original articles published in peerreviewed English-language journals since 2015. Based on keywords, 198 studies were identified and screened for eligibility. Ultimately, the review analyzed 25 articles including 16 that assessed the effects of prenatal exposure to pyrethroids on children's neurobehavioural development, 3 studies that assessed the effects on the course and outcome of pregnancy, and further 3 focused on respiratory disease. In addition, 1 study analyzed the development of obesity and 2 studies examined the effects on children's growth, weight and body composition in early childhood. In conclusion, there is considerable uncertainty about the adverse effects of prenatal exposure to pyrethroids on children's health. The strongest evidence has been reported for neurobehavioural development although results are also inconsistent. Further research is needed to understand the mechanisms of action and health effects of pyrethroids in susceptible populations. Int J Occup Med Environ Health. 2024;37(4).

Placental Sonomorphologic Appearance and Fetomaternal Outcome in Fontan Circulation.

Objectives: Pregnancies in women with Fontan circulation are on the rise, and they are known to imply high maternal and fetal complication rates. The altered hemodynamic profile of univentricular circulation affects placental development and function. This study describes placental sonomorphologic appearance and Doppler examinations and correlates these to histopathologic findings and pregnancy outcomes in women with Fontan circulation. Methods: A single-center retrospective analysis of pregnancies in women with Fontan circulation was conducted between 2018 and 2023. Maternal characteristics and obstetric and neonatal outcomes were recorded. Serial ultrasound examinations including placental sonomorphologic appearance and Doppler studies were assessed. Macroscopic and histopathologic findings of the placentas were reviewed. Results: Six live births from six women with Fontan physiology were available for analysis. Prematurity occurred in 83% (5/6 cases) and fetal growth restriction and bleeding events in 66% (4/6 cases) each. All but one placenta showed similar sonomorphologic abnormalities starting during the late second trimester, such as thickened globular shape, inhomogeneous echotexture, and hypoechoic lakes, resulting in a jelly-like appearance. Uteroplacental blood flow indices were within normal range in all women. The corresponding histopathologic findings were non-specific and consisted of intervillous and subchorionic fibrin deposition, villous atrophy, hypoplasia, or fibrosis. Conclusions: Obstetric and perinatal complication rates in pregnancies of women with Fontan circulation are high. Thus, predictors are urgently needed. Our results suggest that serial ultrasound examinations with increased awareness of the placental appearance and its development, linked to the Doppler sonographic results of the uteroplacental and fetomaternal circulation, may be suitable for the early identification of cases prone to complications.

The Impact of Fetal Growth Restriction on Prenatal 2D Ultrasound and Doppler Study of the Fetal Adrenal Gland.

Background: Uteroplacental insufficiency in fetuses with growth restriction (FGR) leads to chronic hypoxia and stress, predominantly affecting the adrenal glands. However, the mechanisms of impact remain unclear. Objectives: This study is aimed at comparing the Doppler indices of the adrenal artery and the adrenal gland sizes between FGR and those with normal growth. Materials and Methods: A multicenter, cross-sectional study was conducted from February to December 2023. We compared 34 FGR to 34 with normal growth in terms of inferior adrenal artery (IAA) Doppler indices and adrenal gland volumes. Results: The IAA peak systolic velocity (PSV) in the FGR group was 14.9 ± 2.9 cm/s compared to 13.5 ± 2.0 cm/s in the normal group, with a mean difference of 1.4 cm/s (95% confidence interval [CI]: 0.27-2.65; p value = 0.017). There were no significant differences between groups in terms of IAA pulsatility index (PI), resistance index (RI), or systolic/diastolic (S/D), with p values of 0.438, 0.441, and 0.658, respectively. The volumes of the corrected whole adrenal gland and the corrected neocortex were significantly larger in the FGR group, with p values of 0.031 and 0.020, respectively. Conclusion: Both increased IAA PSV and enlarged volumes of the corrected whole adrenal gland and neocortex were found in fetuses with FGR, suggesting significant adrenal gland adaptation in response to chronic intrauterine stress.

Mitochondrial dysfunction and oxidative stress in selective fetal growth restriction.

INTRODUCTION: Placental dysfunction is the primary cause of selective fetal growth restriction (sFGR), and the specific role of mitochondria remains unclear. This study aims to elucidate mitochondrial functional defects in sFGR placentas and explore the roles of mitochondrial genomic and epigenetic alterations in its pathogenesis. METHODS: The placental villi of MCDA twins with sFGR were collected and the morphology and number of mitochondria were observed by transmission electron microscopy. Meanwhile, the levels of reactive oxygen species (ROS), ATP and oxidative damage markers were assessed. Mitochondrial DNA (mtDNA) copy number detection, targeted sequencing and methylation sequencing were performed. The expression of placental cytochrome c oxidase subunit I (COX I) and mitochondrial long non-coding RNAs (lncRNAs) were evaluated by Western blotting and qPCR. RESULTS: Compared with placentae from normal fetuses, pronounced mitochondrial damage within cytotrophoblast was revealed in sFGR placentae, alongside augmented mitochondrial number in syncytiotrophoblast. Enhanced oxidative stress in these placentae was evidenced by elevated markers of oxidative damage, accompanied by increased ROS production and diminished ATP generation. In sFGR placentae, a notable rise in mitochondrial copy number and one heterozygous mutation in the MT-RNR2 gene were observed, along with decreased COX Ⅰ levels, increased lncND5, lncND6, lncCyt b, and MDL1 synthesis, and decreased RMRP synthesis. DISCUSSION: Findings collectively confirmed an exacerbation of oxidative stress within sFGR placentae, coinciding with mitochondrial dysfunction, compromised energy production, and ultimately the failure of compensatory mechanisms to restore energy balance, which may result from mutations in the mitochondrial genome and abnormal expression of epigenetic regulatory genes.

Fetal weight growth trajectories and childhood development: A population-based cohort study.

This study aimed to investigate whether fetal growth trajectories (FGTs) could predict early childhood development, indicate intrauterine metabolic changes, and explore potential optimal and suboptimal FGTs. FGTs were developed by using an unsupervised machine-learning approach. Children's neurodevelopment, anthropometry, and respiratory outcomes in the first 6 years of life were assessed at different ages. In a subgroup of participants, we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs. We identified 6 FGTs: early decelerating, early decelerating with late catch-up growth, early accelerating, early accelerating with late medium growth, late decelerating, and late accelerating. The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development, mental development, intelligence quotient, and lung function and a lower risk of behaviour and respiratory problems. Compared with the optimal FGT, early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function, while early accelerating FGT was associated with more severe autistic symptoms, poor lung function, and increased risks of overweight/obesity. Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs, whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT. These findings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism. The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease, but further research on related mechanisms is still needed.

Amniotic-umbilical-to-cerebral ratio, a Doppler index for estimating adverse perinatal outcomes in fetal growth restriction.

OBJECTIVE: To evaluate amniotic fluid volume with Doppler parameters and its association with composite adverse perinatal outcomes (CAPOs) in fetal growth restriction (FGR). MATERIALS AND METHODS: This study was conducted prospectively in a tertiary referral center between 2023 and 2024 on pregnant women diagnosed with early- and late-onset FGR. Fetal ultrasonographic measurements, including deepest vertical pocket (DVP) for amniotic fluid, and Doppler parameters including uterine artery (UtA) systolic/diastolic (S/D) and pulsatility index (PI), middle cerebral artery (MCA) S/D and PI, and umbilical artery (UA) S/D and PI, were conducted following fetal biometry. The cerebroplacental ratio (CPR), cerebral ratio, cerebro-placental-uterine ratio (CPUR), and amniotic-umbilical-to-cerebral ratio (AUCR) were all calculated. Pregnant women diagnosed with FGR were planned to give birth after 37 weeks' gestation, unless a pregnancy complication requiring earlier delivery occurred. We assessed perinatal outcomes subsequent to delivery, with CAPOs defined as the presence of at least one adverse outcome: 5th minute APGAR score <7, respiratory distress syndrome (RDS), umbilical cord blood pH <7.2, and neonatal intensive care unit (NICU) admission. RESULTS: The study included 132 participants, divided into early- (n = 32) and late-onset FGR (n = 100) groups. AUCR was significantly lower in fetuses with late-onset FGR who experienced CAPOs. Multivariate analysis showed gestational age at birth and birth weight were significant predictors of CAPOs in early-onset FGR, while gestational age, birth weight, and AUCR were significant predictors in late-onset FGR. CPR, UCR, and CPUR did not show significance in predicting CAPOs in both early- and late-onset FGR on multivariate analysis. CONCLUSIONS: AUCR is a potential reliable marker for predicting adverse perinatal outcomes in late-onset FGR.

Clinical value of prenatal screening markers in early pregnancy combined with perinatal characteristics to predict fetal growth restriction.

Background: Due to the incomplete standardization of the etiology and diagnostic criteria for fetal growth restriction (FGR), there has been uncertainty in the early prediction of FGR. The comprehensive estimation of FGR was mainly based on various factors, such as maternal characteristics and medical history, nuchal translucency (NT), and serum biochemical markers [pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (free ß-hCG)]. Herein, we performed a retrospective cohort study to investigate the correlation and diagnostic value of maternal markers such as PAPP-A, free ß-hCG, and NT in the first trimester with maternal characteristics, so as to provide theoretical basis for perinatal care and the application of low-dose aspirin. Methods: A retrospective cohort study was conducted to analyze the data of an FGR group and a non-FGR group. Chi-square test and Mann-Whitney U test were used for univariate analysis of qualitative or quantitative data, respectively. Modified Poisson regression calculated the relative risk (RR) and 95% confidence interval (CI) of perinatal variables; P<0.05 was considered statistically significant. Results: The multiple of median (MoM) of PAPP-A level and NT in the FGR group were lower than those of the non-FGR group [0.63 (0.12-2.08) vs. 1.01 (0.28-2.41) MoM, 1.30 (0.80-2.07) vs. 1.40 (0.80-2.20) cm, P<0.05]. The weight, score, and length of newborns in the FGR group were lower than those in the non-FGR group (all P<0.001). Modified Poisson regression analysis showed that gestational hypertension (GH) [RR =1.836 (95% CI: 1.188-2.836)], oligohydramnios [1.420 (95% CI: 1.022-1.973)], premature rupture of membranes (PROM) [0.641 (95% CI: 0.425-0.969)], female infant [1.539 (95% CI: 1.098-2.157)], low infant length [5.700 (95% CI: 3.416-9.509)], low birth weight [1.609 (95% CI: 1.012-2.559), and increased PAPP-A MoM [0.533 (95% CI: 0.369-0.769)] were associated with FGR. The cut-off value of PAPP-A + free ß-hCG + NT for predicting FGR was 0.190, with a sensitivity of 0.547 and a specificity of 0.778. Conclusions: Early screening markers combined with perinatal characteristics have better diagnostic value in predicting FGR and provide a scientific basis for the clinical use of low-dose aspirin to prevent FGR.

Bioengineering approaches for patient-specific analysis of placenta structure and function.

The leading cause of perinatal mortality is fetal growth restriction (FGR), defined as in utero fetal growth below the 10th percentile. Insufficient exchange of oxygen and nutrients at the maternal-fetal interface is associated with FGR. This transport occurs through the vasculature of the placenta, particularly in the terminal villi, where the vascular membranes have a large surface area and are the thinnest. Altered structure of the placenta villi is thought to contribute to decreased oxygen exchange efficiency, however, understanding how the three-dimensional microstructure and properties decrease this efficiency remains a challenge. Here, a novel, multiscale workflow is presented to quantify patient-specific biophysical properties, 3D structural features, and blood flow of the villous tissue. Namely, nanoindentation, optical coherence tomography, and ultrasound imaging were employed to measure the time-dependent material properties of placenta tissue, the 3D structure of villous tissue, and blood flow through the villi to characterize the microvasculature of the placenta at increasing length scales. Quantifying the biophysical properties, the 3D architecture, and blood flow in the villous tissue can be used to infer changes in maternal-fetal oxygen transport at the villous membrane. Overall, this multiscale understanding will advance knowledge of how microvascular changes in the placenta ultimately lead to FGR, opening opportunities for diagnosis and intervention.

Utilizing Repetitive Serial Placental Ultrasounds for Diagnosing a Massive Subchorionic Thrombohematoma: Insights Into Soluble FMS-Like Tyrosine Kinase-1/Placental Growth Factor (sFlt-1/PlGF) Trends.

The patient, a 34-year-old primigravida with no prior medical history, presented at 23 + 0 weeks with gestational hypertension and fetal growth restriction (FGR). Ultrasound examination showed a placental mass, and subsequent repeated ultrasound scans revealed changes in the mass' echogenicity, raising suspicion of a massive subchorionic thrombohematoma (MST). While the blood pressure was mildly elevated without proteinuria and organ dysfunctions, serum soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratios showed significantly elevated values. A cesarean section was performed at 29 + 2 weeks due to the nonreassuring fetal status. The female infant, with Apgar scores of 1/1 at one/five minutes and an umbilical artery pH of 7.16, remained unresponsive and died seven hours postdelivery. Pathology examination revealed a massive hematoma in the subchorionic space, measuring 22 mm thick, directly beneath the umbilical cord attachment. This case underscores the importance of repetitive placental ultrasound in MST diagnosis and suggests the potential utility of sFlt-1/PlGF ratios in predicting adverse outcomes.

Confined placental mosaicism with trisomy 13 complicated by severe preeclampsia: A case report and literature review.

A 31-year-old primiparous woman underwent non-invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t-statistics (Z-score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development.

Relative uteroplacental insufficiency of labor.

Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.

Prediction of intrapartum fetal compromise at the end of pregnancy; is Doppler, and not weight, that matters.

Despite the fact that labor depends on too many interacting factors and no parameter can fully predict its outcome, fetal cerebral Doppler has emerged as the most reliable tool for prediction, in contrast with fetal weight, which performs significantly worse in the last weeks of pregnancy. The importance of the cerebral Doppler follows the inverse pathway of fetal weight increasing its performance in the last weeks of pregnancy and reaching its highest ability prior to labor. A combination of cerebral flow, fetal weight, and selected clinical information may obtain moderate predictions of labor outcome, provided the interval to labor is not long.

Maternal Innate Immune Reprogramming After Complicated Pregnancy.

PROBLEM: Preeclampsia (PE) and fetal growth restriction (FGR) are often associated with maternal inflammation and an increased risk of cardiovascular and metabolic disease in the affected mothers. The mechanism responsible for this increased risk of subsequent disease may involve reprogramming of innate immune cells, characterized by epigenetic modifications. METHOD OF STUDY: Circulating monocytes from women with PE, FGR, or uncomplicated pregnancies (control) were isolated before labor. Cytokine release from monocytes following exposure to lipopolysaccharide (LPS) and the presence of lysine 4-trimethylated histone 3 (H3K4me3) within TNF promoter sequences were evaluated. Single-cell transcriptomic profiles of circulating monocytes from women with PE or uncomplicated pregnancies were assessed. RESULTS: Monocytes from women with PE or FGR exhibited increased IL-10 secretion and decreased IL-1ß and GM-CSF secretion in response to LPS. While TNFα secretion was not significantly different in cultures of control monocytes versus those from complicated pregnancies with or without LPS exposure, monocytes from complicated pregnancies had significantly decreased levels of H3K4me3 associated with TNF promoter sequences. Cluster quantification and pathway analysis of differentially expressed genes revealed an increased proportion of anti-inflammatory myeloid cells and a lower proportion of inflammatory non-classical monocytes among the circulating monocyte population in women with PE. CONCLUSIONS: Monocytes from women with PE and FGR exhibit an immune tolerance phenotype before initiation of labor. Further investigation is required to determine whether this tolerogenic phenotype persists after the affected pregnancy and contributes to increased risk of subsequent disease.

Advanced magnetic resonance imaging in human placenta: insights into fetal growth restriction and congenital heart disease.

Placental function plays a crucial role in fetal development, as it serves as the primary interface for delivery of nutrients and oxygen from the mother to fetus. Magnetic resonance imaging (MRI) has significantly improved our ability to visualize and understand the placenta's complex structure and function. This review provides an up-to-date examination of the most common and novel placental MRI techniques. It will also discuss the clinical applications of MRI in diagnosing and monitoring placental insufficiency, as well as its implications for fetal growth restriction (FGR) and congenital heart disease (CHD). Ongoing research using multi-parametric MRI techniques aims to develop novel biomarkers and uncover the relationships between placental parameters and pre-onset diseased states, ultimately contributing to better maternal and fetal health outcomes, which is essential to better guide clinical judgement.

A customised fetal growth and birthweight standard for Qatar: a population-based cohort study.

OBJECTIVES: Customized birthweight centiles have improved the detection of small for gestational age (SGA) and large for gestational age (LGA) babies compared to existing population standards. This study used perinatal registry data to derive coefficients for developing customized growth charts for Qatar. METHODS: The PEARL registry data on women delivering in Qatar (2017-2018) was used to develop a multivariable linear regression model predicting optimal birthweight. Physiological variables included gestational age, maternal height, weight, ethnicity, parity, and sex of the baby. Pathological variables such as hypertension, preexisting and gestational diabetes and smoking were calculated and excluded to derive the optimal weight at term. RESULTS: The regression model found a term optimal birthweight of 3,235 g for a Qatari nationality mother with median height (159 cm), booking weight (72 kg), parity (1) and gestation at birth (276 days) at the end of an uncomplicated pregnancy. Constitutional coefficients significantly affecting birthweight were gestational age, height, weight, and parity. The main pathological factors were preexisting diabetes (increase by +175.7 g) and smoking (decrease by -190.9 g). The SGA and LGA rates in the entire cohort after applying the population-specific customized centiles were 11.1 and 12.2 %, respectively (contrasting with the Hadlock standard: SGA-26.3 % and LGA-1.8 %, and Fenton standard: SGA-12.9 % and LGA-4.0 %). CONCLUSIONS: Constitutional and pathological variations in fetal growth and birthweight apply in the maternity population in Qatar and have been quantified to allow the generation of customised charts for better identification of pregnancies with abnormal growth. Currently in-use population standards may misdiagnose many SGA and LGA babies.

The association between maternal fruit consumption before and during pregnancy and fetal growth: The Lanzhou birth cohort study.

Background: The association between maternal fruit consumption and fetal growth remains inconsistent. The current study aimed to determine whether maternal fruit consumption was associated with low birth weight (LBW) or small for gestational age (SGA) babies. Methods: A large birth cohort study was conducted in Lanzhou, China, from 2010 to 2012 and included 10,076 pregnant women at the 1st, 2nd, and 3rd trimester of pregnancy for analysis. Fruit consumption in the 1st, 2nd, and 3rd trimester of pregnancy was measured by a self-designed food frequency questionnaire (FFQ) and divided into three groups: 1) inadequate fruit consumption: <200 g/d for the1st, 2nd, and 3rd trimester; 2) adequate fruit consumption: 200-350 g/d for the 1st trimester or 200-400 g/d for the 2nd and 3rd trimester; 3) excessive fruit consumption: >350 g/d for the 1st trimester or > 400 g/d for the 2nd and 3rd trimester. A case-control study was used to analyze the association between fruit intake during pregnancy and low birth weight infants. Results: Compared to adequate fruit consumption, excessive fruit consumption throughout each trimester of pregnancy was associated with a lower risk of LBW, with an odds ratio (OR) ranging from 0.70 to 0.79 (95 % confidence interval, CI: 0.57-0.98); while inadequate fruit consumption was associated with a higher risk of infant LBW, with an OR ranging from 1.26 to 1.36 (95%CI: 1.04-1.66). After stratifying by mother's pre-pregnancy body mass index (BMI), the results were similar among women with underweight BMI. No significance was found between fruit consumption and SGA in the general population. Still, stratified analyses showed that inadequate fruit consumption was associated with an increased risk of SGA in underweight mothers, with an OR ranging from 1.66 to 1.79 (95%CI: 1.13-2.64). Conclusions: Fruit consumption during pregnancy reduces the risk of LBW in Chinese women, especially in women with low pre-pregnancy BMI.

Does Catch-Up Growth Come with a Cognitive Cost? Cognitive Outcome and Growth Patterns in Growth Discordant Identical Twins.

OBJECTIVE: To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth. STUDY DESIGN: This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17 years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2 years was calculated as (weight [kg] at 2 years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2 years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent. RESULTS: Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with ß-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P < .0001). Adjusted for birth weight z score and gestational age, CUG in the first 2 years after birth was not significantly associated with FSIQ (ß-coefficient 0.108 [95% CI -1.373 to 1.590], P = .886). CONCLUSIONS: Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development.