Search

Babies born with fetal growth restriction (FGR) are at higher risk of developing cardiometabolic diseases across the life course. The reduction in substrate supply to the developing fetus that causes FGR not only alters cardiac growth and structure but may have deleterious effects on metabolism and function. Using a sheep model of placental restriction to induce FGR, we investigated key cardiac metabolic and functional markers that may be altered in FGR. We also employed phase‐contrast magnetic resonance imaging MRI to assess left ventricular cardiac output (LVCO) as a measure of cardiac function. We hypothesized that signalling molecules involved in cardiac fatty acid utilisation and contractility would be impaired by FGR and that this would have a negative impact on LVCO in the late gestation fetus. Key glucose (GLUT4 protein) and fatty acid (FATP, CD36 gene expression) substrate transporters were significantly reduced in the hearts of FGR fetuses. We also found reduced mitochondrial numbers as well as abundance of electron transport chain complexes (complexes II and IV). These data suggest that FGR diminishes metabolic and mitochondrial capacity in the fetal heart; however, alterations were not correlated with fetal LVCO. Overall, these data show that FGR alters fetal cardiac metabolism in late gestation. If sustained ex utero, this altered metabolic profile may contribute to poor cardiac outcomes in FGR‐born individuals after birth. Key points: Around the time of birth, substrate utilisation in the fetal heart switches from carbohydrates to fatty acids. However, the effect of fetal growth restriction (FGR) on this switch, and thus the ability of the fetal heart to effectively metabolise fatty acids, is not fully understood.Using a sheep model of early onset FGR, we observed significant downregulation in mRNA expression of fatty acid receptors CD36 and FABP in the fetal heart. FGR fetuses also had significantly lower cardiac mitochondrial abundance than controls.There was a reduction in abundance of complexes II and IV within the electron transport chain of the FGR fetal heart, suggesting altered ATP production.This indicates reduced fatty acid metabolism and mitochondrial function in the heart of the FGR fetus, which may have detrimental long‐term implications and contribute to increased risk of cardiovascular disease later in life. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is associated with cardiovascular and respiratory complications after birth and beyond. Despite research showing a range of neurological changes following FGR, little is known about how FGR affects the brainstem cardiorespiratory control centres. The primary neurons that release serotonin reside in the brainstem cardiorespiratory control centres and may be affected by FGR. At two time points in the last trimester of sheep brain development, 110 and 127 days of gestation (0.74 and 0.86 of gestation), we assessed histopathological alterations in the brainstem cardiorespiratory control centres of the pons and medulla in early‐onset FGR versus control fetal sheep. The FGR cohort were hypoxaemic and asymmetrically growth restricted. Compared to the controls, the brainstem of FGR fetuses exhibited signs of neuropathology, including elevated cell death and reduced cell proliferation, grey and white matter deficits, and evidence of oxidative stress and neuroinflammation. FGR brainstem pathology was predominantly observed in the medullary raphé nuclei, hypoglossal nucleus, nucleus ambiguous, solitary tract and nucleus of the solitary tract. The FGR groups showed imbalanced brainstem serotonin and serotonin 1A receptor abundance in the medullary raphé nuclei, despite evidence of increased serotonin staining within vascular regions of placentomes collected from FGR fetuses. Our findings demonstrate both early and adaptive brainstem neuropathology in response to placental insufficiency. Key points: Early‐onset fetal growth restriction (FGR) was induced in fetal sheep, resulting in chronic fetal hypoxaemia.Growth‐restricted fetuses exhibit persistent neuropathology in brainstem nuclei, characterised by disrupted cell proliferation and reduced neuronal cell number within critical centres responsible for the regulation of cardiovascular and respiratory functions. Elevated brainstem inflammation and oxidative stress suggest potential mechanisms contributing to the observed neuropathological changes.Both placental and brainstem levels of 5‐HT were found to be impaired following FGR. [ABSTRACT FROM AUTHOR]

Introduction: Labor induction exhibits considerable variations in protocols and medication regimens. Limited studies compare vaginal dinoprostone inserts with different oral misoprostol dosages, considering parity influence. This study explores the distinctions among 10 mg vaginal dinoprostone inserts and oral misoprostol 25 μg every 2 and every 4 h for labor induction, stratified by parity. Material and Methods: This retrospective cohort study involved 607 participants across two hospitals. The primary outcome, time from induction to delivery, and secondary outcomes, including mode of delivery and maternal and fetal safety, were assessed. Results: Patient characteristics revealed differences in indication for labor induction, with the dinoprostone cohort having fewer post‐term and premature rupture of membranes cases but more intrauterine growth restriction/small‐for‐gestational age. Both oral misoprostol regimens showed a shorter time to delivery interval compared to the dinoprostone cohort (median: 1380 min [IQR 1381.0] and 1127.0 min [IQR 1214.0] vs 1631.5 [IQR 1736.2], p < 0.001 and p = 0.014). Only the difference between oral misoprostol q2h and vaginal dinoprostone remained significant for nulliparous but not multiparous women, losing significance over all the population after adjusting for confounding factors. The proportion of women giving birth within 24 h did not significantly differ between misoprostol q2h and dinoprostone after adjusting for confounders. When comparing misoprostol q4h with dinoprostone after confounder adjustment, an increased time to delivery interval for misoprostol q4h was found (p = 0.001). Both oral misoprostol regimens exhibited fewer meconium‐stained liquor (miso q4h: OR 0.44, miso q2h: OR 0.34) and cesarean sections (miso q4h: OR 0.48, miso q2h: OR 0.53) compared to dinoprostone, even after adjustment for confounders. Conclusions: Our study suggests that oral misoprostol 25 μg q4h is less effective than 10 mg vaginal dinoprostone for labor induction if parity and indication for induction are adjusted for, particularly in multiparous women. In terms of side effects, oral misoprostol regimens seem superior to vaginal dinoprostone. Our data support the individualized use of different agents for labor induction according to parity, indication for induction, bishop score, and women's preference. [ABSTRACT FROM AUTHOR]

Objective Error in birthweight prediction by sonographic estimated fetal weight (EFW) has clinical implications, such as avoidable cesarean or misclassification of fetal risk in labor. We aimed to evaluate optimal timing of ultrasound and which fetal measurements contribute to error in fetal ultrasound estimations of birth size at the extremes of birthweight. Study Design We compared differences in head circumference (HC), abdominal circumference (AC), femur length, and EFW between ultrasound and corresponding birth measurements within 14 (n = 1,290) and 7 (n = 617) days of birth for small- (SGA, <10th percentile), appropriate- (AGA, 10th–90th), and large-for-gestational age (LGA, >90th) newborns. Results Average differences between EFW and birthweight for SGA neonates were: −40.2 g (confidence interval [CI]: −82.1, 1.6) at 14 days versus 13.6 g (CI: −52.4, 79.7) at 7 days; for AGA, −122.4 g (−139.6, −105.1) at 14 days versus −27.2 g (−50.4, −4.0) at 7 days; and for LGA, −242.8 g (−306.5, −179.1) at 14 days versus −72.1 g (−152.0, 7.9) at 7 days. Differences between fetal and neonatal HC were larger at 14 versus 7 days, and similar to patterns for EFW and birthweight, differences were the largest for LGA at both intervals. In contrast, differences between fetal and neonatal AC were larger at 7 versus 14 days, suggesting larger error in AC estimation closer to birth. Conclusion Using a standardized ultrasound protocol, SGA neonates had ultrasound measurements closer to actual birth measurements compared with AGA or LGA neonates. LGA neonates had the largest differences between fetal and neonatal size, with measurements 14 days from delivery showing 3- to 4-fold greater differences from birthweight. Differences in EFW and birthweight may not be explained by a single fetal measurement; whether estimation may be improved by incorporation of other knowable factors should be evaluated in future research. Key Points Ultrasound measurements may be inadequate to predict neonatal size at birth. Birthweight estimation error is higher for neonates >90th percentile. There is higher error in AC closer to birth. [ABSTRACT FROM AUTHOR]

Aim: We review evidence for effects of physical activity before and during gestation on the course of pregnancy and ask if there are circumstances where physical activity can stress the fetus due to competition for oxygen and energy substrates. Results: We first summarize physiological responses to exercise in nonpregnant people and known physiological adaptations to pregnancy. Comparing the two, we conclude that physical activity prior to and continuing during gestation is beneficial to pregnancy outcome. The effect of starting an exercise regimen during pregnancy is less easy to assess as few studies have been undertaken. Results from animal models suggest that the effects of maternal exercise on the fetus are transient; the fetus can readily compensate for a short‐term reduction in oxygen supply. Conclusion: In general, we conclude that physical activity before and during pregnancy is beneficial, and exercise started during pregnancy is unlikely to affect fetal development. We caution, however, that there are circumstances where this may not apply. They include the intensive exercise regimens of elite athletes and pregnancies at high altitudes where hypoxia occurs even in the resting state. [ABSTRACT FROM AUTHOR]

• In our study, cerebral fissure measurements of healthy fetuses between 20–24 weeks of gestation were obtained. • Normal reference values were determined for these anatomical structures, which are closely related to fetal cortical development. • All four main fissures examined in our study were found to enlarge with advancing gestational age. • The reference intervals we obtained will be helpful for clinicians interested in neurosonography. • Cerebral fissure measurements may provide additional information about actual gestational age and cortical maturation. We aimed to establish normal reference ranges for insula, sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF) measured by prenatal ultrasonography (USG) between 20–24 weeks of gestation in healthy fetuses. A total of 186 fetuses in the second trimester were evaluated by transabdominal USG. All measurements were obtained by a single clinician. The study was divided into four subgroups (Group A: 20–20 weeks six days, Group B: 21–21 weeks six days, Group C: 22–22 weeks six days, Group D: 23–23 weeks six days). Eight fetuses (4.23 %) between 20 and 21 weeks of gestation could not be included in the study because the sulcus borders could not be clearly evaluated. Measurements were obtained in all fetuses over 21 weeks of gestation. Reference ranges were obtained for insula, SF, POF, and CF in all fetuses and subgroups. At 20 and 23 weeks and six days gestation, mean insula depth was 14.96 ± 1.62 mm (min 11.0 mm − max 18.9 mm), mean SF depth was 6.96 ± 1.35 mm (min 3.6 mm − max 10.0 mm), mean POF depth was 2.05 ± 0.66 mm (min 1.1 mm − max 5.6 mm) and mean CF depth was 2.42 ± 0.68 mm (min 1.5 mm − 6.1 mm). There was a correlation between the cerebellum and cisterna magna and all fissure depths. Our nomograms of healthy fetuses may be helpful in the early detection of cortical maturation abnormalities. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the normative courses of pregnancy‐related anxiety throughout pregnancy and their antecedents. We examined in a large scale pregnancy cohort which potentially distinct trajectories of pregnancy‐related anxiety across pregnancy can be identified, and which factors predict these trajectories. Methods: A general sample of pregnant women (n = 2928) from the FinnBrain Birth Cohort participated in this study. Several questionnaires were filled in at 14, 24, and 34 weeks of gestation, including the pregnancy‐related anxiety questionnaire‐revised as main outcome. Latent Growth Mixture Modeling was applied to identify the trajectories of pregnancy‐related anxiety across pregnancy, and t‐tests and chi‐quare tests were conducted to find antecedents of these trajectories. Results: Two distinct trajectories were identified: (1) a low symptoms group, N = 2594 (88.6%), with lower and slightly increasing levels of pregnancy‐related anxiety (2) a moderately‐high symptoms group, N = 334 (11.4%) reported higher and slightly decreasing levels of anxiety. Correlates of the moderately‐high anxious group included a lower monthly income, drinking alcohol or smoking in early pregnancy, more daily hassles and less joy, more early life adversities, younger age, primiparity, single parenthood, using depression medication, and having higher scores on depression and general anxiety. Conclusions: Although the majority of pregnant women fall within a low risk trajectory of pregnancy‐related anxiety, another group with consistently higher levels of pregnancy anxiety throughout pregnancy may need more clinical attention, as their high pregnancy‐related anxiety scores may indicate a risk profile that includes a variety of general and more pregnancy‐specific risk factors, which together can negatively affect fetal and infant development and behavior. [ABSTRACT FROM AUTHOR]

• Human iPSC neural progenitor cells (NPC) only respond to IL-6 by trans -signalling. • Microglia-secreted sIL6Ra levels insufficient to induce NPC IL-6 trans -signalling. • NPC display marginal transcriptional responses to IL-6 in co-culture with microglia. • There are clear and replicable effects of IL-6 on the microglial transcriptome. • Future work should explore the role of IL-6 cis- and trans -signalling in microglia. Elevated interleukin (IL-)6 levels during prenatal development have been linked to increased risk for neurodevelopmental disorders (NDD) in the offspring, but the mechanism remains unclear. Human-induced pluripotent stem cell (hiPSC) models offer a valuable tool to study the effects of IL-6 on features relevant for human neurodevelopment in vitro. We previously reported that hiPSC-derived microglia-like cells (MGLs) respond to IL-6, but neural progenitor cells (NPCs) in monoculture do not. Therefore, we investigated whether co-culturing hiPSC-derived MGLs with NPCs would trigger a cellular response to IL-6 stimulation via secreted factors from the MGLs. Using N=4 donor lines without psychiatric diagnosis, we first confirmed that NPCs can respond to IL-6 through trans -signalling when recombinant IL-6Ra is present, and that this response is dose-dependent. MGLs secreted soluble IL-6R, but at lower levels than found in vivo and below that needed to activate trans -signalling in NPCs. Whilst transcriptomic and secretome analysis confirmed that MGLs undergo substantial transcriptomic changes after IL-6 exposure and subsequently secrete a cytokine milieu, NPCs in co-culture with MGLs exhibited a minimal transcriptional response. Furthermore, there were no significant cell fate-acquisition changes when differentiated into post-mitotic cultures, nor alterations in synaptic densities in mature neurons. These findings highlight the need to investigate if trans -IL-6 signalling to NPCs is a relevant disease mechanism linking prenatal IL-6 exposure to increased risk for psychiatric disorders. Moreover, our findings underscore the importance of establishing more complex in vitro human models with diverse cell types, which may show cell-specific responses to microglia-released cytokines to fully understand how IL-6 exposure may influence human neurodevelopment. [ABSTRACT FROM AUTHOR]

The proper function of the placenta is essential for the health and growth of the fetus and the mother. The placenta relies on dynamic gene expression for its correct and timely development and function. Although numerous studies have identified genes vital for placental functions, equine placental molecular research has primarily focused on single placental locations, in sharp contrast with the broader approach in human studies. Here, we hypothesized that the molecular differences across different regions of the equine placenta are negligible because of its diffuse placental type with a macroscopic homogenous distribution of villi across the placental surface. We compared the transcriptome and stereological findings of the body, pregnant horn, and non-pregnant horn within the equine chorioallantois. Our transcriptomic analysis indicates that the variation between regions of the placenta within individuals is less than the variation observed between individuals. A low number of differentially expressed genes (DEGs) (n = 8) was identified when comparing pregnant and non-pregnant horns within the same placenta, suggesting a remarkable molecular uniformity. A higher number of DEGs was identified when comparing each horn to the body (193 DEGs comparing pregnant horn with body and 207 DEGs comparing non-pregnant horn with body). Genes with a higher expression in the body were associated with processes such as extracellular matrix synthesis and remodeling, which is relevant for placental maturation and placenta-endometrial separation at term and implies asynchrony of these processes across locations. The stereological analysis showed no differences in microcotyledonary density, and width between the locations. However, we observed a greater chorioallantoic thickness in the body and pregnant horn compared to the non-pregnant horn. Overall, our findings reveal a uniform transcriptomic profile across the placental horns, alongside a more distinct gene expression pattern between the uterine body and horns. These regional differences in gene expression suggest a different pace in the placental maturation and detachment among the placental locations. [Display omitted] • Gene expression variation observed across different placental locations. • Genes related to ECM degradation vary between the body and horns. • Microscopic features are uniform across the entire placenta. [ABSTRACT FROM AUTHOR]

• PPE inhibited the development of glomeruli and promoted compensatory growth of renal tubules. • PPE at clinical dose disturbed fetal kidney development with a time-effect difference, manifested as full-term pregnancy exposure > early pregnancy exposure > mid-late pregnancy exposure. • The developmental toxicity of PPE on fetal kidney was more serious to the female fetuses than the males. Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication. Now, it is also recognized as an emerging environmental contaminant. Pregnant women may be exposed to prednisone actively or passively through multiple pathways and cause developmental toxicity to the fetus. However, the impact of prenatal prednisone exposure (PPE) on fetal kidney development remains unclear. In this study, pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses (0.25, 0.5, or 1 mg/(kg·day)), or at the dose of 1 mg/(kg·day) in different gestational days (GD) (GD0-9, GD10-18, or GD0-18). The pregnant mice were euthanized on GD18. HE staining revealed fetal kidney dysplasia, with an enlarged glomerular Bowman's capsule space and a reduced capillary network in the PPE groups. The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups. However, overall gene expression in renal tubules and collecting ducts were markedly increased. All of the above effects were more pronounced in high-dose, full-term pregnancy, and female fetuses. Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2, increased the expression of Hnf1β, Hnf4α, and Wnt9b, and inhibited the expression of glial cell line-derived neurotrophic factor (GDNF) and Notch signaling pathways. In conclusion, this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney, and the time effect is manifested as full-term pregnancy > early pregnancy > mid-late pregnancy. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective To analyze risk factors (maternal, obstetric and demographic) associated with congenital syphilis and the clinical characteristics of the newborns. Method A cross-sectional study carried out in ten public maternity hospitals in Fortaleza, Ceará, Brazil that included cases of live births reported with congenital syphilis in 2015. Results 469 cases were analyzed; 199 (42.4 %) showed some sign or symptom suggestive of congenital syphilis; of these, 65 (32.7 %) were preterm, 87 (43.7 %) had low birth weight, 116 (58.3 %) had jaundice that required phototherapy, 13 (6.5 %) had hepatomegaly, 10 (5 %) had skin lesions, eight (4.0 %) had splenomegaly and one (0.5 %) had limb pseudoparalysis. Records of other clinical changes were identified in 36 (7.7 %) children. Children whose mothers were not treated or who received a drug other than penicillin and those whose mothers had a VDRL titer ≥ 1:16 at birth were 3.7 and 3.2 times more likely to be born with signs of congenital syphilis (p < 0.001- 95 % CI 2.41–5.58; p < 0.001 – 95 % CI 2.41–5.58) respectively. Conclusions The findings of this study draw attention to the importance of improving the quality of prenatal care and the development of studies aimed at finding alternative drugs for the treatment of syphilis in pregnant women and the prevention of congenital syphilis. [ABSTRACT FROM AUTHOR]

Craniofacial morphology is extremely diversified within bat phylogeny, however growth and development of the palate in bats remains unstudied. The formation of both midline and bilateral orofacial clefts in laryngeally echolocating bats, morphologically similar to the syndromic and non‐syndromic cleft palate in humans, are not well understood. Developmental series of prenatal samples (n = 128) and adults (n = 10) of eight bat species (two pteropodids, four rhinolophoids, and two yangochiropterans), and two non‐bat mammals (Mus musculus and Erinaceus amurensis), were CT‐scanned and cranial bones forming the upper jaw complex were three‐dimensionally visualised to assess whether differences in palate development can be observed across bat phylogeny. Volumetric data of bones composing the upper jaw complex were measured to quantify palate growth. The premaxilla is relatively reduced in bats compared to other mammals and its shape is heterogeneous depending on the presence and type of orofacial cleft across bat phylogeny. The palatine process of premaxillary bones is lacking in pteropodids and yangochiropterans, whereas the premaxilla is a mobile structure which is only in contact caudally with the maxilla by a fibrous membrane or suture in rhinolophoids. In all bats, maxillary bones progressively extend caudally and palatine bones, in some cases split into three branches, extend caudally so that they are completely fused to another one medially prior to the birth. Ossification of the vomer and fusion of the maxillary and palatine bones occur earlier in rhinolophoids than in pteropodids and yangochiropterans. The vomer ossifies bilaterally from two different ossification centres in yangochiropterans, which is uncommon in other bats and non‐bat mammals. Analysis of ontogenetic allometric trajectories of the upper jaw complex revealed faster development of maxillary, vomer, and palatine bones in yangochiropterans compared to other bats, especially rhinolophoids. Ancestral state reconstruction revealed that yangochiropterans have a higher magnitude of change in ossification rate compared to other bats and E. amurensis a lower magnitude compared to M. musculus and bats. This study provides new evidence of heterochronic shifts in craniofacial development and growth across bat phylogeny that can improve understanding of the developmental differences characterising nasal and oral emission strategies. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions To assess the validity of the Fetal Medicine Foundation (FMF) chorionicity‐specific models for fetal growth in twin pregnancy.This was an external validation study of the FMF models using a nationwide Danish cohort of twin pregnancies. The cohort included all dichorionic (DC) and monochorionic diamniotic (MCDA) twin pregnancies with an estimated delivery date between 2008 and 2018, which satisfied the following inclusion criteria: two live fetuses at the first‐trimester ultrasound scan (11–14 weeks' gestation); biometric measurements available for the calculation of estimated fetal weight (EFW) using the Hadlock‐3 formula; and delivery of two liveborn infants. Validation involved assessing the distributional properties of the models and estimating the mean EFW Z‐score deviations. Additionally, the models were applied to pregnancies that delivered preterm and attended non‐scheduled visits (complicated pregnancies).Overall, 8542 DC and 1675 MCDA twin pregnancies met the inclusion criteria. In DC twins, 17 084 fetuses were evaluated at a total of 95 346 ultrasound scans, of which 44.5% were performed at scheduled visits in pregnancies carried to 37 + 0 weeks or later. The median number of growth scans per DC twin fetus from 20 + 0 weeks onwards was four. The model showed good agreement with the validation cohort for scheduled visits in DC twins delivered at 37 + 0 weeks or later (mean EFW Z‐score, –0.14 ± 1.05). In MCDA twins, 3350 fetuses underwent 31 632 eligible ultrasound scans, of which 59.5% were performed at scheduled visits in pregnancies carried to 36 + 0 weeks or later. The median number of growth scans per MCDA twin fetus from 16 + 0 weeks onwards was 10. The model showed favorable agreement with the validation cohort for scheduled visits in MCDA twins delivered at 36 + 0 weeks or later (mean EFW Z‐score, –0.09 ± 1.01). Non‐scheduled visits and preterm delivery before 37 + 0 weeks for DC twins and before 36 + 0 weeks for MCDA twins corresponded with smaller weight estimates, which was consistent with the study's definition of complicated pregnancy.The FMF models provide a good fit for EFW measurements in our Danish national cohort of uncomplicated twin pregnancies assessed at routine scans. Therefore, the FMF models establish robust criteria for subsequent investigations and potential clinical applications. Future research should focus on exploring the consequences of clinical implementation, particularly regarding the identification of twins that are small‐for‐gestational age, as they are especially susceptible to adverse perinatal outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (n = 34,725; 45–82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bimodal distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex, and complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (n = 228; 21–36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes. [Display omitted] • A pipeline is provided to extract 5 phenotypes for each of 40 sulci from brain MRI • Sulcal phenotype networks consistently find an axis of linear to complex shape • Adult sulcal complexity is linked to heritability, function, and fetal sulcation • Linear sulci demarcate zones of expression for developmentally enriched genes Snyder et al. develop measures of human cortical folding, revealing an axis of linear to complex sulcal shape across the adult cortex. This axis predicts the phased emergence of sulci in utero and boundaries of cortical gene expression, implicating these processes in the formation of mature cortical geometry. [ABSTRACT FROM AUTHOR]

Background: Ultrasound technology is indispensable in perinatal care due to its non-invasive and painless nature, offering vital insights into foetal development and childbirth. With the academisation of midwifery in Germany, there is a growing necessity to incorporate ultrasound training into midwifery education. This paper discusses the development and implementation of an introductory obstetric ultrasound curriculum tailored for midwifery students, focusing on fundamental ultrasound techniques in obstetrics. Materials and methods: We used Kern's six-step approach of curricular development comprising [1] problem identification and general needs assessment [2], needs assessment of the targeted learners [3], goals and objectives [4], educational strategies [5], implementation, and [6] evaluation and feedback. The individual components of the curriculum were meticulously designed based on comprehensive literature reviews, thorough consultations with experienced ultrasound experts and evaluated needs of participants prior to the course instruction. Results: Twenty-seven ultrasound-naive midwifery students participated in the newly developed obstetric ultrasound course. Structured as a modular and integrated framework, the course aimed to provide theoretical and practical instruction in basic obstetric ultrasound, with intrapartum sonography and focused assessment with abdominal sonography for trauma (FAST) as key supplementary specialisations. The results demonstrated a significant increase in the students' overall knowledge and practical skills, as evidenced by the median post-course total score rising from 20 to 60 out of 75 (p < 0.001) in the objective structured clinical examination (OSCE) and from 9 to 19 out of 20 (p = 0.001) in the knowledge test. Additionally, students reported high satisfaction with the course and noted substantial personal benefits. Conclusion: The integration of basic obstetric ultrasound training within the midwifery curriculum is feasible and effective to teach fundamental knowledge and skills of obstetric ultrasound examinations to midwifery students. Expansion, standardisation and regulatory structures are critical components for a continued improvement and realistic integration into midwifery educational frameworks and thus the further development of the midwifery profession. [ABSTRACT FROM AUTHOR]

Fetal teratomas, though rare, represent a significant proportion of tumors arising during fetal development. These tumors arise from pluripotent cells and can present in varying degrees of severity, ranging from incidental findings to life-threatening conditions. Prenatal imaging, via ultrasound and MRI, is necessary for diagnosis and risk assessment. The management of fetal teratomas, particularly those associated with complications like hydrops or airway obstruction, often requires a multidisciplinary approach. Interventions such as ex-utero intrapartum treatment (EXIT) procedures and minimally invasive alternatives have emerged as critical tools to improve neonatal outcomes in severe cases. Despite advances in fetal therapies, careful prenatal monitoring and individualized management remain essential, especially for tumors with high vascularity or those that risk compromising cardiac output. This review explores the diagnostic methods, management strategies, and outcomes associated with fetal teratomas, highlighting recent advancements that contribute to improving survival and reducing morbidity in affected neonates. [ABSTRACT FROM AUTHOR]

Background: The trophoblast is a significant source of vitamin D synthesis during pregnancy, with the literature suggesting its role in fetal growth. We aim to underline a possible mechanism that would explain negative fetal outcomes in COVID-19-positive mothers by examining the relationship between altered placental structure and function and throphoblast cells' vitamin D receptor levels. Methods: The study included 170 placental samples collected from women who gave birth at term without complications, divided into three groups: COVID-19-positive and unvaccinated, COVID-19-negative and vaccinated, and COVID-19-negative and unvaccinated, with exclusion criteria for any other medical complications. Immunohistochemistry (IHC) was performed to detect vitamin D receptor (VDR) expression, and immediate fetal outcomes (weight and Apgar score) were assessed. Results: We found lower gestational age at birth, lower birth weight, and reduced placental VDR (vitamin D receptor) levels in COVID-19-positive women compared to COVID-19-vaccinated and COVID-19-negative women. Conclusions: The presence of the vitamin D receptor in the placenta is related to fetal and placental growth. Its deficiency may contribute to negative fetal outcomes in COVID-19-positive cases. [ABSTRACT FROM AUTHOR]

Objective: To generate longitudinal fetal growth data in an Indian population and compare it with Intergrowth-21st. Material and methods: Fetal biometry data was collected in a prospective longitudinal observational study (REVAMP: Research Exploring Various Aspects and Mechanisms in Preeclampsia) from 2017 to 2022. Fetal crown-rump length (CRL) was measured at 11–14 weeks gestation, and biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) at 18–22 and 32–35 weeks, and converted into Z-scores using the Intergrowth standard. Generalized Additive Models for Location, Scale and Shape (GAMLSS) models were used to construct fetal growth centile curves compared against Intergrowth centiles. Results: Out of 1096 singleton pregnancies in REVAMP, this analysis included 655 'healthy' pregnancies (uncomplicated by pre-eclampsia, diabetes, pre-term delivery or low birth weight) and a sub-set of 106 'low-risk' pregnancies defined using Intergrowth criteria. The 'healthy' study subjects showed lower mean CRL Z-score [-0.45 SD (95% CI:-0.54,-0.37)] at 11–14 weeks, and BPD Z-score [-1.2 SD (-1.28,-1.11) and -1.17 SD (-1.23,-1.1)] at 18–22 and 32–35 weeks respectively. Mean HC Z-score was comparable to the Intergrowth standard at 18–22 weeks [-0.08 SD (-0.16, 0.02)] but smaller at 32–35 weeks [-0.25 SD (-0.32,-0.19)]. Mean AC Z-score was lower at 18–22 weeks [-0.32 SD (-0.41,-0.23)] but comparable at 32–35 weeks [0.004 SD (-0.07, 0.07)]. FL was comparable to or larger than the Intergrowth standard at both time points [0.05 SD (-0.05, 0.14); 0.82 SD (0.75, 0.89), respectively]. These findings were similar, though measurements were slightly larger, in the 'low-risk' sample. Conclusions: This data from healthy and low-risk pregnant women in urban western India indicates that some fetal dimensions and growth trajectories differ significantly from the Intergrowth-21st. Our data suggest the need for a larger representative study to define a population-specific fetal growth reference for India, for identification of fetal growth restriction. [ABSTRACT FROM AUTHOR]

To investigate whether assisted reproductive technology (ART) affects gross fetal movement. A prospective cohort study. 65 women who conceived with ART (ART group) and 211 women (control group) without ART recorded fetal movement with the fetal movement acceleration measurement recorder at night weekly after 28 weeks. The number ratio of 10 s epochs with fetal movement to all epochs was calculated as the fetal movement parameter. When no fetal movement was observed for more than 5 min, it was defined as a no fetal movement period, and the average number per hour, the average duration, and the longest duration of the no fetal movement periods were calculated as the no fetal movement parameters. Gestational weeks were classified into 28–33 and 34–39 weeks, and the fetal movement parameter and the no fetal movement parameters were compared using the Student's t-test. The fetal movement parameters at 28–33 weeks were 17.43% (ART) and 16.58% (control) (p = 0.219), and those at 34–39 weeks were 11.72% (ART) and 11.96% (control) (p = 0.590). In the same way, for the no fetal movement parameters, the average numbers were 1.58 and 1.63 per hour (p = 0.357), and 2.36 and 2.30 per hour (p = 0.503). The average durations were 8.30 and 8.46 min (p = 0.712), and 9.20 and 9.51 min (p = 0.188). The longest durations were 16.26 and 17.02 min (p = 0.295), and 22.34 and 22.87 min (p = 0.534). ART does not affect gross fetal movement count. [ABSTRACT FROM AUTHOR]

Interleukin‐4 (IL‐4)/IL‐4 receptor alpha (IL‐4Rα) signalling pathways play important roles in the complex process of bone formation and bone remodelling. However, whether IL‐4/IL‐4Rα participates in skeletogenesis during embryonic development is not completely understood. We used the anti‐IL‐4Rα monoclonal antibody (anti‐IL‐4Rα mAb) as a powerful investigational tool to evaluate the potential roles of IL‐4/IL‐4Rα in the chondrogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. Simultaneously, we explored the effect of IL‐4/IL‐4Rα on bone ossification during rat embryo‐fetal development. In this study, we found that, compared to the control group, IL‐4 can significantly promote the chondrogenic differentiation of BMSCs. Furthermore, following exposure to anti‐IL‐4Rα mAb in pregnant rats, unexpected phenomena were observed in fetal bone development, including non‐ossification of the fetal sternum, an incomplete ossification centre in long bones and a reduced number of ossification points in digit (toe) bones. To further investigate the underlying mechanism of the phenotype, we studied the rat sternum as the target organ, starting from different time points of sternum development in the embryonic stage. The results indicated that the retardation mainly occurred in the middle and late stages of embryonic development. This retardation was characterized by the inhibition of the differentiation process of mesenchymal stem cells into chondrocytes, resulting in reduced angiogenesis near the ossification centre, failure of osteoblasts to invade the centre of the cartilage body with the blood vessels and delayed formation of the primary ossification centre (POC). Overall, our study demonstrated the significant function of IL‐4/IL‐4Rα in chondrogenic differentiation of BMSCs and bone ossification during embryo‐fetal development. [ABSTRACT FROM AUTHOR]

Neural organoids have emerged as valuable tools for studying the developing brain, sparking enthusiasm and driving their adoption in disease modeling, drug screening, and investigating fetal neural development. The increasing popularity of neural organoids as models has led to a wide range of methodologies aimed at continuous improvement and refinement. Consequently, research groups often improve and reconfigure protocols to create region-specific organoids, resulting in diverse phenotypes, including variations in morphology, gene expression, and cell populations. While these improvements are exciting, routine adoptions of such modifications and protocols in the research laboratories are often challenging due to the reiterative empirical testing necessary to validate the cell types generated. To address this challenge, we systematically compare the similarities and differences that exist across published protocols that generates subpallial-specific organoids to date. In this review, we focus specifically on exploring the production of major GABAergic neuronal subtypes, especially Medium Spiny Neurons (MSNs) and Interneurons (INs), from multiple subpallial organoid protocols. Importantly, we look to evaluate the cell type diversity and the molecular pathways manipulated to generate them, thus broadening our understanding of the existing subpallial organoids as well as assessing the in vitro applicability of specific patterning factors. Lastly, we discuss the current challenges and outlook on the improved patterning of region-specific neural organoids. Given the critical roles MSN and IN dysfunction play in neurological disorders, comprehending the GABAergic neurons generated by neural organoids will undoubtedly facilitate clinical translation. [ABSTRACT FROM AUTHOR]

Arachnoid cysts (ACs) are frequently encountered as incidental findings in the brain, with most cases being asymptomatic and not requiring intervention. However, severe brain malformations caused by ACs are rare. In this study, we describe the case of an 8-day-old female infant with a left mandibular mass that was diagnosed as an insular operculum, which has become disconnected and herniated into the parapharyngeal space through an incompletely ossified greater wing of the sphenoid, caused by a fetal Galassi Type III AC. The newborn also exhibited left hearing impairment, which did not improve at the 6-month follow-up after the cyst peritoneal shunt. This report highlights that ACs that manifest during the early fetal period may protrude from the cranial cavity through an unossified skull, potentially affecting the development of brain tissues. [ABSTRACT FROM AUTHOR]

Objective: To generate longitudinal fetal growth data in an Indian population and compare it with Intergrowth-21st. Material and methods: Fetal biometry data was collected in a prospective longitudinal observational study (REVAMP: Research Exploring Various Aspects and Mechanisms in Preeclampsia) from 2017 to 2022. Fetal crown-rump length (CRL) was measured at 11–14 weeks gestation, and biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) at 18–22 and 32–35 weeks, and converted into Z-scores using the Intergrowth standard. Generalized Additive Models for Location, Scale and Shape (GAMLSS) models were used to construct fetal growth centile curves compared against Intergrowth centiles. Results: Out of 1096 singleton pregnancies in REVAMP, this analysis included 655 'healthy' pregnancies (uncomplicated by pre-eclampsia, diabetes, pre-term delivery or low birth weight) and a sub-set of 106 'low-risk' pregnancies defined using Intergrowth criteria. The 'healthy' study subjects showed lower mean CRL Z-score [-0.45 SD (95% CI:-0.54,-0.37)] at 11–14 weeks, and BPD Z-score [-1.2 SD (-1.28,-1.11) and -1.17 SD (-1.23,-1.1)] at 18–22 and 32–35 weeks respectively. Mean HC Z-score was comparable to the Intergrowth standard at 18–22 weeks [-0.08 SD (-0.16, 0.02)] but smaller at 32–35 weeks [-0.25 SD (-0.32,-0.19)]. Mean AC Z-score was lower at 18–22 weeks [-0.32 SD (-0.41,-0.23)] but comparable at 32–35 weeks [0.004 SD (-0.07, 0.07)]. FL was comparable to or larger than the Intergrowth standard at both time points [0.05 SD (-0.05, 0.14); 0.82 SD (0.75, 0.89), respectively]. These findings were similar, though measurements were slightly larger, in the 'low-risk' sample. Conclusions: This data from healthy and low-risk pregnant women in urban western India indicates that some fetal dimensions and growth trajectories differ significantly from the Intergrowth-21st. Our data suggest the need for a larger representative study to define a population-specific fetal growth reference for India, for identification of fetal growth restriction. [ABSTRACT FROM AUTHOR]

ABSTRACT SGSM proteins are small modulator proteins interacting with proteins in the RAS signaling pathway. Studies with mouse and human tissues indicated that SGSM genes were highly expressed in the brain and could be expressed at different levels at different stages of development in fetal and adult brain tissue. It was first reported by Birnbaum et al. that the SGSM3 gene might be associated with a Mendelian inherited disease in families of Ashkenazi Jews with clinical manifestations of intellectual disability (ID). In this study, a novel homozygous stop‐gain (NM_015705.6: c.1576C>T: p.(Arg526Ter)) variation was detected in the SGSM3 gene in two siblings with short stature and ID findings. The report of two cases with bi‐allelic LOF variants in the SGSM3 gene from different populations with similar clinical manifestations strengthens the potential of this gene as a candidate gene for the nonsyndromic ID phenotype. Functional studies are required to investigate the signaling pathways affected by SGSM3 gene variations to produce the ID phenotype and their effect on the functioning of neurons. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions Maternal socioeconomic status (SES) is an important predictor of adverse birth outcomes and postnatal health across global populations. Chronic inflammation is implicated in cardiometabolic disease risk in high‐income contexts and is a potential pathway linking maternal adversity to offspring health trajectories. To clarify how socioeconomic inequality shapes pregnancy inflammation in middle‐income settings, we investigated SES as a predictor of inflammatory cytokines in late gestation in a sample from the Cebu Longitudinal Health Nutrition Survey in Cebu, Philippines.We used multiple regression to evaluate maternal SES, reflected in household assets, as a predictor of general inflammation (C‐reactive protein), inflammatory cytokines (interleukin‐6, interleukin‐10), and inflammatory balance (n = 407). Inflammatory markers were measured at 29.9 weeks gestation in dried blood spots, and a measure reflecting relative balance of IL6 and IL10 was calculated to capture pro‐ versus anti‐inflammatory skewed immune profiles.Greater household assets significantly predicted lower IL6 concentration (p <  0.001), with a trend toward lower IL6 relative to IL10 (p = 0.084). C‐reactive protein and IL10 were not individually related to SES.The inverse relationship between SES and pregnancy inflammation in Cebu is consistent with results from high‐income settings. These findings further highlight the influence of socioeconomic conditions on immune regulation during pregnancy. Given the evidence that gestational inflammation impacts offspring fetal growth, our results suggest that social and economic effects on immune function may be an important pathway for the intergenerational transmission of health disparities. [ABSTRACT FROM AUTHOR]

Background: Progressive oxidative stress easily occurs as a result of a gradual increase in the intensity of maternal metabolism due to rapid foetal development and increased intensity of lactation. However, studies on the effects of processive oxidative stress on nutrient transport in the placenta have received little attention. The present study was conducted on sows at 85 days of gestation to study the effects of pterostilbene (PTE) on maternal oxidative stress status and placental nutrient transport. Results: PTE increased the antioxidant capacity and immunoglobulin content in mothers' blood and milk, reduced the level of inflammatory factors, and improved the nutrient content of milk. PTE also reduced sow backfat loss and the number of weak sons, and increased piglet weaning weight and total weaning litter weight. We subsequently found that PTE enhanced placental glucose and fatty acid transport and further affected glycolipid metabolism by increasing the expression of LAL, PYGM, and Gbe-1, which activated the PI3K phosphorylation pathway. Moreover, PTE addition altered the relative abundance of the Firmicutes, Proteobacteria, Parabacillus, and Bacteroidetes-like RF16 groups in sow faeces. PTE increased the levels of acetate, propionate, butyrate and isovalerate in the faeces. Conclusions: These findings reveal that the addition of PTE during pregnancy and lactation mitigates the effects of processive oxidative stress on offspring development by altering maternal microbial and placental nutrient transport capacity. [ABSTRACT FROM AUTHOR]

This study was carried out on pregnant uteruses obtained from healthy Hair goats (Capra aegagrus hircus). A total of thirteen pregnant uteruses, six second and seven third trimesters, were used. Morphometrically, placentome numbers, lengths, widths and depths were measured. Randomly selected placentomes from the second and third trimesters were stained with the triple staining method. Caruncular and cotyledonary areas, capillary numbers and areas were measured using Qupath v0.5.0 software. The Minitab (version 21.4.1) was used for statistical analysis. While no statistical difference was observed in the number of placentomes between trimesters (p > 0.05), placentome length, width and depth were higher in the third trimester compared to the second trimester (p < 0.001). No difference was observed in the number of caruncular and cotyledonary capillaries in the second trimester. In the second trimester, the caruncular capillary area was higher than the cotyledonary capillary area (p < 0.05). Both caruncular and cotyledonary capillary area parameters were higher in the third trimester than in the second trimester (p < 0.001). In the third trimester, the caruncular capillary area was higher than the cotyledonary capillary area (p < 0.001). The number of caruncular capillaries and cotyledonary capillaries was statistically significantly higher in the third trimester compared to the second trimester. In addition, the number of cotyledonary capillaries was higher than that of caruncular capillaries in the third trimester (p < 0.001). A positive and significant correlation was found between the day of pregnancy and the number of placentomes in the second trimester (p < 0.05). No correlation was observed between the day of pregnancy and the number of placentomes in the third trimester. Vascular area density showed a faster development in foetal tissue than in maternal tissue. Placentome size and angiogenesis increased with the progression of pregnancy. [ABSTRACT FROM AUTHOR]

Based on an interview study with Danish women, this article explores how the frequent use of pregnancy mobile applications shapes the lived or experienced pregnancy. More specifically, we look at a reported dilemma between, on one hand, using the information of pregnancy apps on bodily and fetal developments to gain a sense of control over individual pregnancies and, on the other hand, an experience of the apps becoming something of a controlling factor in the lives of pregnant women. Respondents reported that the information of the apps created different kinds of concerns and that they became almost obsessed with comparing their own symptoms with the apps' standardized information on what they could expect to experience at specific stages of the pregnancy. Our analysis draws on a socio-material perspective that acknowledges the ability of technology to enact certain kinds of experiences and shape concerns. We argue that the power of the apps (so to speak) is related, in part to the abundance of information they provide, which may contribute to a sensation of never knowing enough, but also in part to the use of apps becoming an integrated part of everyday cell phone routines. [ABSTRACT FROM AUTHOR]

Aim: To construct birthweight charts customised for maternal height and evaluate the effect of customization on SGA and LGA classification. Methods: Data were extracted (n = 21 350) from the MiCaS project in the Netherlands (2012–2020). We constructed the MiCaS‐birthweight chart customised for maternal height using Hadlock's method. We defined seven 5‐centimetre height categories from 153 to 157 cm until 183–187 cm and calculated SGA and LGA prevalences for each category, using MiCaS and current Dutch birthweight charts. Results: The MiCaS‐chart showed substantially higher birthweight values between identical percentiles with increasing maternal height. In the Dutch birthweight chart, not customised for maternal height, the prevalence of SGA (p90) increased with increasing height category, from 1.4% in the lowest height category to 21.8% in the highest category (range 20.4%). In the MiCaS‐birthweight chart, SGA and LGA prevalences were more constant across maternal heights, similar to overall prevalences (SGA range 3.3% and LGA range 1.7%). Conclusion: Compared to the current Dutch birthweight chart, the MiCaS‐birthweight chart customised for maternal height shows a more even distribution of SGA and LGA prevalences across maternal heights. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the associations of plasma polybrominated diphenyl ether (PBDE) concentrations in early pregnancy with gestational weight gain (GWG). Design: Prospective cohort study. Setting: US‐based, multicentre cohort of pregnant women. Population: We used data from 2052 women without obesity and 397 women with obesity participating in the NICHD Fetal Growth Studies – Singleton Cohort, with first‐trimester plasma PBDE concentrations and weight measurements throughout pregnancy. Methods: We applied generalised linear models and Bayesian kernel machine regression (BKMR) to evaluate both the individual and joint associations of PBDEs with measures of GWG, adjusting for potential confounders. Main outcome measures: Total GWG (kg), total and trimester‐specific GWG velocities (kg/week), and GWG categories and trajectory groups. Results: Mean pre‐pregnancy BMIs were 23.6 and 34.5 kg/m2 for women without and with obesity, respectively. Among women without obesity, there were no associations of PBDEs with any GWG measure. Among women with obesity, one standard deviation increase in log‐transformed PBDE 47 was associated with a 1.87 kg higher total GWG (95% CI 0.39–3.35) and a 0.05 kg/week higher total GWG velocity (95% CI 0.01–0.09). Similar associations were found for PBDE 47 in BKMR among women with obesity, and PBDE 47, 99 and 100 were associated with lower odds of being in the low GWG trajectory group. Conclusions: PBDEs were not associated with GWG among individuals without obesity. Among those with obesity, only PBDE 47 showed consistent positive associations with GWG measures across multiple statistical methods. Further research is needed to validate this association and explore potential mechanisms. [ABSTRACT FROM AUTHOR]

Intrauterine development is crucial for life-long health; therefore, elucidation of its key regulators is of interest for their potential prognostic and therapeutic implications. Originally described as a membrane-bound anti-aging protein, Klotho has evolved as a regulator of numerous functions in different organ systems. Circulating Klotho is generated by alternative splicing or active shedding from cell membranes. Recently, Klotho was identified as a regulator of placental function, and while Klotho does not cross the placental barrier, increased levels of circulating α-Klotho have been identified in umbilical cord blood compared with maternal blood, indicating that Klotho may also play a role in intrauterine development. In this narrative review, we discuss novel insights into the specific functions of the Klotho proteins in the placenta and in intrauterine development, while summarizing up-to-date knowledge about their structures and functions. Klotho plays a role in stem cell functioning, organogenesis and haematopoiesis. Low circulating maternal and foetal levels of Klotho are associated with preeclampsia, intrauterine growth restriction, and an increased perinatal risk for newborns, indicating a potential use of Klotho as biomarker and therapeutic target. Experimental administration of Klotho protein indicates a neuro- and nephroprotective potential, suggesting a possible future role of Klotho as a therapeutic agent. However, the use of Klotho as intervention during pregnancy is as yet unproven. Here, we summarize novel evidence, suggesting Klotho as a key regulator for healthy pregnancies and intrauterine development with promising potential for clinical use. [ABSTRACT FROM AUTHOR]

The pig is the most widely consumed domestic animal in China, providing over half of the meat supply in food markets. For livestock, a key economic trait is the reproductive performance, which is significantly influenced by placental development. The placenta, a temporary fetal organ, is crucial for establishing maternal–fetal communication and supporting fetal growth throughout pregnancy. DNA methylation is an epigenetic modification that can regulate the gene expression by recruiting proteins involved in gene silencing or preventing transcription factor binding. To enhance our understanding of the molecular mechanisms underlying DNA methylation in porcine placental development, this review summarizes the structure and function of the porcine placenta and the role of DNA methylation in placental development. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate whether primed anoestrus mares are suitable recipients for embryos produced by intracytoplasmic sperm injection (ICSI). Anoestrus was confirmed in four mares and daily doses of oestradiol benzoate (6 mg in total) over 5 days were administered; after 3 days of rest, oral altrenogest was administered at 0.088 mg/kg and embryos (1 to 5 embryos per mare; 15 in total) were transferred 3.5 days after progesterone onset. Uterine lavage was conducted 48 h after transfer. The results revealed an 80% embryo recovery rate, and among the retrieved embryos, 67% showed evident intrauterine development. Hence, ICSI‐derived embryos can be successfully transferred to primed anoestrus mares, but more studies are required to ensure further embryo development and foaling. [ABSTRACT FROM AUTHOR]

AbstractObjective: To determine the role of sortilin in the pathogenesis of fetal growth restriction (FGR) by examining serum sortilin levels in fetal cord blood. Methods: This prospective case-control study was conducted at Ankara Etlik City Hospital between July 2023 and January 2024. Group 1 included 44 pregnant women with late FGR; Group 2 included 44 healthy pregnant women as controls. Results: Umbilical cord blood sortilin levels were significantly higher in the FGR group [2.96 (2.43–4.01)] compared to the control group [2.12 (1.74–3.18)] (p = 0.001). Sortilin levels negatively correlated with APGAR scores at 1 min (r=-0.281, p = 0.008) and 5 min (r=-0.292, p = 0.006). A sortilin threshold of 2.58 ng/ml predicted composite adverse neonatal outcomes with 66.7% sensitivity, 53.1% specificity, and an AUC of 0.652 (95% CI: 0.529–0.775, p = 0.031). Conclusion: This study showed that sortilin levels, which are indicators of oxidation, were higher in the cord blood of newborns with late FGR. [ABSTRACT FROM AUTHOR]

There is evidence that transcription factor (TF) encoding genes, which temporally control development in multiple cell types, can have tens of enhancers that regulate their expression. The NR2F1 TF developmentally promotes caudal and ventral cortical regional fates. Here, we epigenomically compared the activity of Nr2f1's enhancers during mouse cortical development with their activity in a transgenic assay. We identified at least six that are likely to be important in prenatal cortical development, with three harboring de novo mutants identified in ASD individuals. We chose to study the function of two of the most robust enhancers by deleting them singly or together. We found that they have distinct and overlapping functions in driving Nr2f1's regional and laminar expression in the developing cortex. Thus, these two enhancers, probably in combination with the others that we defined epigenetically, precisely tune Nr2f1's regional, cell type, and temporal expression during corticogenesis. [ABSTRACT FROM AUTHOR]

PACS (phosphofurin acidic cluster sorting) proteins are known for their roles in sorting cargo proteins to organelles and can physically interact with WD40 repeat-containing protein WDR37. PACS1, PACS2, and WDR37 variants are associated with multisystemic syndromes and neurodevelopmental disorders characterized by intellectual disability, seizures, developmental delays, craniofacial abnormalities, and autism spectrum disorder. However, the functional effects of syndromic variants at the cellular level remain unknown. Here, we report the expression pattern of Caenorhabditis elegans orthologs of PACS and WDR37 and their interaction. We show that cePACS-1 and ceWDR-37 colocalize to somatic cytoplasm of many types of cells and are mutually required for expression, supporting a conclusion that the intermolecular dependence of PACS1/PACS2/PACS-1 and WDR37/WDR-37 is evolutionarily conserved. We further show that editing in PACS1 and PACS2 variants in cePACS-1 changes protein localization in multiple cell types, including neurons. Moreover, expression of human PACS1 can functionally complement C. elegans PACS-1 in neurons, demonstrating conserved functions of the PACS–WDR37 axis in an invertebrate model system. Our findings reveal effects of human variants and suggest potential strategies to identify regulatory network components that may contribute to understanding molecular underpinnings of PACS/WDR37 syndromes. [ABSTRACT FROM AUTHOR]

Objectives: Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier‐related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction. Materials and Methods: A CAL‐27‐LEC co‐culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability. Western blotting and RT‐qPCR detected protein and mRNA expression under different conditions, respectively. CCK‐8, scratch wound healing, and transwell assays revealed cell migration and proliferation. Tube formation experiment tested capacity for endothelial tube formation. Immunohistochemical staining analyzed tissue sections from 43 oral cancer individuals with/without diabetes. Results: In high‐glucose co‐culture system, we observed increased lymphatic barrier permeability and decreased expression of ZO‐1 and occludin, two tight‐junction proteins; conversely, the expression of PAR2, a high permeability‐related protein, was increased. Following linagliptin treatment, the expression levels of VEGF‐C, VEGFR‐3, and PAR2 decreased, while those of ZO‐1 and occludin increased. Considerably higher levels of LYVE‐1 expression in individuals with diabetes than in those without diabetes. Conclusions: By ameliorating the high glucose‐induced disruption of the lymphatic endothelial barrier, linagliptin may reduce lymphangiogenesis and exhibit an inhibitory effect on lymphatic metastasis in oral cancer patients with diabetes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the epidemiological and three‐dimensional (3D) radiological characterizations of odontomas, as well as the spatial relationship between odontomas and gubernaculum tracts (GT). Materials and Methods: We retrieved the cone‐beam computed tomography (CBCT) data of 87,590 patients. Dentition, location, type, diameter of the odontomas, width of the dental follicle (DF), the spatial relationship between the odontoma and GT, and the influence on adjacent teeth were evaluated. Results: Significant differences were found in age, dentition, location, Max/Min diameter, width of DF, impaction, retention, and root bending of adjacent teeth among different spatial relationships between the odontoma and GT (all p < 0.05), as well as in age, type and size, absence, impaction, malposition, and retention of adjacent teeth among different locations of odontomas (all p < 0.05). Compared to the odontomas without impaction, those with impaction had larger diameter (p < 0.05 in all directions). This statistically significant association was consistent for odontomas with malposition, while no similar result was observed in the maximum diameter. Conclusion: Our findings provide the preliminary data for clinicians to comprehensively understand the incidence, radiographic characterizations and symptoms of odontoma in Chinese population. [ABSTRACT FROM AUTHOR]

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. 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. 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 %). 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. [ABSTRACT FROM AUTHOR]

Aim: The objective of this meta‐analysis was to evaluate obstetric outcomes in gestational diabetes mellitus (GDM) patients treated with flexible management based on intrauterine ultrasound fetal growth (FMIUFG) or strict maternal glycemic adjustment (SMGA). Methods: We performed a comprehensive systematic review of electronic databases for randomized clinical trials (RCTs) comparing obstetrics outcomes of singleton GDM patients managed according to FMIUFG or SMGA. The review protocol was registered in PROSPERO (CRD497888). Searches were conducted in PubMed, Embase, Cochrane, and LILACS. Primary outcomes were gestational age at delivery and birth weight. Random‐effect model meta‐analyses were used to minimize the effects of uncertainty associated with inter‐study variability. Results are reported as standardized mean differences (SMDs) or as odds ratios (ORs) and their 95% confidence interval (CI). Heterogeneity between studies was estimated using the I2 statistic. The Cochrane Risk of Bias Scale was used to assess the quality of studies. There were five RCTs with low to moderate risk of bias, including 450 patients managed according to the FMIUFSG and 381 according to the SMGA. Results: The macrosomia (birthweight >4000 g) rate was lower in pregnancies managed according to FMIUFG than SMGA adjustments (OR: 0.34; 95%CI: 0.16, 0.71). There were no significant differences in hypertensive disorder, cesarean section, neonatal intensive care unit admission, and large newborn for gestational age rates. Conclusions: The macrosomia rate was lower in women managed with the FMIUFG. There were no significant differences in other obstetric and neonate outcomes. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does RXFP2 disruption impair male fertility? SUMMARY ANSWER We identified biallelic variants in RXFP2 in patients with male infertility due to spermatogenic arrest at the spermatid stage, supporting a role of RXFP2 in human spermatogenesis, specifically in germ cell maturation. WHAT IS KNOWN ALREADY Since RXFP2, the receptor for INSL3, plays a crucial role in testicular descent during prenatal development, biallelic variants lead to bilateral cryptorchidism, as described in four families to date. While animal models have also suggested a function in spermatogenesis, the postnatal functions of RXFP2 and its ligand INSL3, produced in large amounts by the testes from puberty throughout adulthood, are largely unknown. STUDY DESIGN, SIZE, DURATION A family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism underwent clinical, endocrinological, histological, genomic, in vitro cellular, and in silico investigations. PARTICIPANTS/MATERIALS, SETTING, METHODS The endocrinological and histological findings were correlated with publicly available single-cell RNA sequencing (scRNA-seq) data. The genomic defects have been characterized using long-read sequencing and validated with in silico modeling and an in vitro cyclic AMP reporter gene assay. MAIN RESULTS AND THE ROLE OF CHANCE An intragenic deletion of exon 1–5 of RXFP2 (NM_130806.5) was detected in trans with a hemizygous missense variant c.229G>A, p.(Glu77Lys). The p.(Glu77Lys) variant caused no clear change in cell surface expression or ability to bind INSL3, but displayed absence of a cAMP signal in response to INSL3, indicating a loss-of-function. Testicular biopsy in the proband showed a maturation arrest at the spermatid stage, corresponding to the highest level of RXFP2 expression in scRNA-seq data, thereby providing a potential explanation for the impaired fertility. LIMITATIONS, REASONS FOR CAUTION Although this is so far the only study of human cases that supports the role of RXFP2 in spermatogenic maturation, this is corroborated by several animal studies that have already demonstrated a postnatal function of INSL3 and RXFP2 in spermatogenesis. WIDER IMPLICATIONS OF THE FINDINGS This study corroborates RXFP2 as gene implicated in autosomal recessive congenital bilateral cryptorchidism due to biallelic variants, rather than autosomal-dominant cryptorchidism due to monoallelic RXFP2 variants. Our findings also support that RXFP2 is essential in human spermatogenesis, specifically in germ cell maturation, and that biallelic disruption can cause male infertility through spermatogenic arrest at the spermatid stage. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by the Bellux Society for Pediatric Endocrinology and Diabetology (BELSPEED) and supported by a Research Foundation Flanders (FWO) senior clinical investigator grant (E.D.B. 1802220N) and a Ghent University Hospital Special Research Fund grant (M.C. FIKO-IV institutional fund). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. WHAT IS KNOWN ALREADY HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. STUDY DESIGN, SIZE, DURATION This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012–2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). PARTICIPANTS/MATERIALS, SETTINGS, METHODS The study included 69 children aged 6–9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. MAIN RESULTS AND THE ROLE OF CHANCE School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. LIMITATIONS, REASONS FOR CAUTION The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. WIDER IMPLICATIONS OF THE FINDINGS This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. STUDY FUNDING/COMPETING INTEREST(S) The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER NCT05168228 [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between varying degrees of abnormality in the Doppler uterine artery pulsatility index (UtA‐PI) and adverse perinatal outcome. Methods: This was a prospective study of women with a singleton, non‐anomalous pregnancy in whom UtA‐PI was measured universally in midpregnancy and who gave birth in Oxford University Hospitals, Oxford, UK, between 2016 and 2023. Relative risk ratios (RRR) for the primary outcomes of extended perinatal mortality and live birth with a severe small‐for‐gestational‐age (SGA) neonate were calculated using multinomial logistic regression, for early preterm birth (before 34 + 0 weeks' gestation) and late preterm/term birth (at or after 34 + 0 weeks). Risks were also investigated for iatrogenic preterm birth and a composite adverse outcome before 34 + 0 weeks. Results: Overall, 33 364 pregnancies were included in the analysis. Compared to those with a normal UtA‐PI, the risk of extended perinatal mortality with delivery before 34 + 0 weeks was higher in women with UtA‐PI ≥ 90th percentile (RRR, 4.7 (95% CI, 2.7–8.0); P < 0.001), but this was not demonstrated in births at or after 34 + 0 weeks. The risk of live birth with severe SGA was associated strongly with abnormal UtA‐PI for early births (RRR, 26.0 (95% CI, 11.6–58.2); P < 0.001) and later births (RRR, 2.3 (95% CI, 1.8–2.9); P < 0.001). Women with raised UtA‐PI were more likely to have an early iatrogenic birth (RRR, 7.8 (95% CI, 5.5–11.2); P < 0.001). For each outcome before 34 + 0 weeks and the composite outcome, the risk increased significantly in association with the degree of abnormality in the UtA‐PI (from < 90th, 90–94th, 95–98th to ≥ 99th percentile) (Ptrend < 0.001). When using the 90th percentile as opposed to the 95th, there was a significant improvement in the overall predictive accuracy (as determined by the area under the receiver‐operating‐characteristics curve) for the composite adverse outcome (χ2 = 6.64, P = 0.01) and iatrogenic preterm birth (χ2 = 4.10, P = 0.04). Conclusions: Elevated UtA‐PI is a key predictor of iatrogenic preterm birth, severe SGA and perinatal loss up to 34 + 0 weeks' gestation. The 90th percentile for UtA‐PI should be used, and management should be tailored according to the degree of abnormality, as pregnancies with very raised UtA‐PI measurement constitute a group at extreme risk of adverse outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low‐dose MSO in the setting of SVP. Methods: This single‐center, open‐label, pilot phase‐1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self‐administered continuous MSO using medical‐grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late‐gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC). Results: Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self‐administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment‐associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head‐circumference‐to‐abdominal‐circumference ratio Z‐scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z‐score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late‐gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z‐score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age. Conclusions: This pilot phase‐1 clinical trial indicates that low‐dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Reproductive phenology is a critical element of how animals persist in their environment and affects survival of young, especially in seasonal environments. We investigated the correlation between fetal eye diameter and birth timing to determine if birthdates could be predicted by a prenatal metric. We used ultrasonography to measure eye diameters of fetuses and vaginal implant transmitters to determine birthdates of Rocky Mountain Bighorn Sheep (Ovis canadensis canadensis) in Wyoming, United States, from 2019 to 2023. Fetal eye diameter strongly predicted days until birth (β = −2.8; pseudo- R 2 = 0.88). Effective prediction of birthdates via ultrasonography can yield opportunities for logistical planning in neonatal studies, monitoring changes in reproductive phenology, and evaluating questions of resource allocation relative to reproductive processes. [ABSTRACT FROM AUTHOR]

Aims/BackgroundDesign/MethodsResultsConclusionRoutine third-trimester ultrasonography is increasingly conducted to screen for foetal growth restriction (FGR) and reduce adverse perinatal and child neurodevelopmental outcomes using timely obstetric management. While it did not reduce adverse perinatal outcomes in previous trials, evidence regarding its association with child neurodevelopmental outcome is absent. We examined whether routine third-trimester ultrasonography is positively associated with child developmental and behavioural/emotional outcomes compared to usual care.Dutch mothers with a low-risk pregnancy participating in a subsample (n = 1070) of a nationwide cluster-randomised trial reported infant (age 6 months) and toddler (age 28 months) developmental milestones (Ages and Stages Questionnaire) and toddlers’ internalising and externalising problems (Child Behavior Checklist). Usual care (n = 380) comprised selective ultrasonography. The intervention strategy (n = 690) included two routine third-trimester ultrasounds next to usual care. Both strategies applied the same interdisciplinary protocol for FGR detection and management.Adjusted linear mixed-level regressions revealed that routine third-trimester ultrasonography was positively but modestly related to z-standardised infant developmental milestones at 6-month follow-up, B = 0.20, 95%CI [0.07; 0.32], p = 0.003, compared to usual care. At 28-month follow-up, these strategies did not differ in child developmental outcome and internalising and externalising problems.Routine third-trimester ultrasonography was positively but modestly associated with infant development. In toddlerhood, routine ultrasonography was not related to child developmental and behavioural/emotional outcomes. Overall, these findings do not support the implementation of routine third-trimester ultrasonography for low-risk pregnant women for reasons concerning children’s early neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The IMPACT BCN trial—a parallel‐group randomized clinical trial where 1221 pregnant women at high risk for small‐for‐gestational age (SGA) newborns were randomly allocated at 19‐ to 23‐week gestation into three groups: Mediterranean diet, Mindfulness‐based Stress reduction or non‐intervention—has demonstrated a positive effect of Mediterranean diet and Stress reduction in the prevention of SGA. However, the mechanism of action of these interventions remains still unclear. The aim of this study is to investigate the effect of Mediterranean diet and Stress reduction on placental volume and perfusion. Material and Methods: Participants in the Mediterranean diet group received monthly individual and group educational sessions, and free provision of extra‐virgin olive oil and walnuts. Women in the Stress reduction group underwent an 8‐week Stress reduction program adapted for pregnancy, consisting of weekly 2.5‐h and one full‐day sessions. Non‐intervention group was based on usual care. Placental volume and perfusion were assessed in a subgroup of randomly selected women (n = 165) using magnetic resonance (MR) at 36‐week gestation. Small placental volume was defined as MR estimated volume <10th centile. Perfusion was assessed by intravoxel incoherent motion. Results: While mean MR placental volume was similar among the study groups, both interventions were associated with a lower prevalence of small placental volume (3.9% Mediterranean diet and 5% stress reduction vs. 17% non‐intervention; p = 0.03 and p = 0.04, respectively). Logistic regression showed that small placental volume was significantly associated with higher risk of SGA in both study groups (OR 7.48 [1.99–28.09] in Mediterranean diet and 20.44 [5.13–81.4] in Stress reduction). Mediation analysis showed that the effect of Mediterranean diet on SGA can be decomposed by a direct effect and an indirect effect (56.6%) mediated by a small placental volume. Similarly, the effect of Stress reduction on SGA is partially mediated (45.3%) by a small placental volume. Results on placental intravoxel incoherent motion perfusion fraction and diffusion coefficient were similar among the study groups. Conclusions: Structured interventions during pregnancy based on Mediterranean diet or Stress reduction are associated with a lower proportion of small placentas, which is consistent with the previously observed beneficial effects of these interventions on fetal growth. [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis. Using a variety of relevant animal models and multiple dose regimens of rHuPH20 across the full spectrum of animal development, we demonstrated that rHuPH20 administration resulted in the formation of ADAs. Although these ADAs can bind both the recombinant rHuPH20 enzyme and recombinant versions of animal model-specific hyaluronidases, they had no impact on fertility parameters (as measured by sperm concentration and motility, litter size, and litter viability) or fetal development. We present the result of our nonclinical studies in order of the developmental lifecycle, beginning with adults. Toxicology studies that extend beyond the standard package are also presented. These studies demonstrate the favorable safety profile of rHuPH20 and ADAs in nonclinical models. Additionally, we identified substantial safety margins for clinically relevant doses of rHuPH20. [Display omitted] • rHuPH20 facilitates subcutaneous administration of therapeutics. • Impact of rHuPH20 and anti-drug antibodies observed in multiple nonclinical models. • rHuPH20 anti-drug antibodies did not negatively alter fertility or development. • Substantial safety margins were identified when compared to human-equivalent doses. • Studies support favorable safety profile of rHuPH20. [ABSTRACT FROM AUTHOR]

The European Board and College of Obstetrics and Gynaecology (EBCOG) and the European Network of Trainees in Obstetrics and Gynaecology (ENTOG) express their concerns on the effect of climate change and environmental pollution. This paper reviews the impact on reproductive health and the contribution to climate change by the field of obstetrics and gynaecology. It concludes that its contributors and the effects of climate change cause definite adverse consequences to fertility and adverse obstetric outcomes. Mankind, and obstetrics and gynaecology personnel as well, must be aware and responsible of its contribution to climate change and consider the impact of their actions and interventions. [ABSTRACT FROM AUTHOR]

The heart is the central organ of the circulatory system, and its proper development is vital to maintain human life. As fetal heart development is complex and poorly understood, we use single-cell RNA sequencing to profile the gene expression landscapes of human fetal hearts from the four-time points: 8, 10, 11, 17 gestational weeks (GW8, GW10, GW11, GW17), and identified 11 major types of cells: erythroid cells, fibroblasts, heart endothelial cells, ventricular cardiomyocytes, atrial cardiomyocytes, macrophage, DCs, smooth muscle, pericytes, neural cells, schwann cells. In addition, we identified a series of differentially expressed genes and signaling pathways in each cell type between different gestational weeks. Notably, we found that ANNEXIN, MIF, PTN, GRN signalling pathways were simple and fewer intercellular connections in GW8, however, they were significantly more complex and had more intercellular communication in GW10, GW11, and GW17. Notably, the interaction strength of OSM signalling pathways was gradually decreased during this period of time (from GW8 to GW17). Together, in this study, we presented a comprehensive and clear description of the differentiation processes of all the main cell types in the human fetal hearts, which may provide information and reference data for heart regeneration and heart disease treatment. [Display omitted] • Gene expression map of human fetal hearts from the four-time points were identified. • Dynamic alteration of cell subpopulations and gene expression during heart development. • ANNEXIN, MIF, PTN, GRN, OSM signalling pathways are crucial in heart development. [ABSTRACT FROM AUTHOR]