Fetal Oxygen Research Articles

Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies

Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment.

Cerebral oxygenation during the period of transition to extrauterine life after natural versus cesarean birth

Objective. We aim to evaluate the implications of cesarean delivery compared to natural birth by analyzing newborns’ systemic and cerebral oxygenation levels during the first 10 minutes of life. Design. This paper presents a 4-year prospective cohort study. Setting. Polizu Maternity, "Alessandrescu-Rusescu" National Institute for Mother and Child's Protection, Bucharest, Romania. Patients. Randomly selected pregnant women and their fetuses. Interventions. During the 10 min following umbilical cord clamping, regional cerebral oxygen saturation (rcSO2) was measured using the INVOS 5100 device and peripheral oxygen saturation (SpO2) was determined using the Masimo SET pulse oximeter in neonates from cesarean and natural deliveries. Main outcome measures. The cerebral fractional tissue oxygen extraction (cFTOE) in the first 10 minutes of life was calculated based on these values. Results. Newborns delivered vaginally showed higher rcSO2 levels at 1 minute of life than those born via C-section (40.5 ± 16.5% vs 33.7 ± 14.8%, AUC = 0.625; IC 95%: 0.506 - 0.743; p = 0.043). Neonatal cFTOE at 1 minute of life was significantly higher in caesarean-delivered newborns versus naturally born neonates (0.40 ± 0.25 vs 0.50 ± 0.19, p = 0.03; AUC = 0.638; IC 95%: 0.517-0.758; p = 0.023). Conclusions. Prelabor cesarean delivery seemingly plays a significant role in the process of fetal and neonatal cerebral oxygenation immediately postnatally, which is highlighted by lower rcSO2 and higher cFTOE values. Cerebral oxygen saturation monitoring in the delivery room allows the optimization of oxygen therapy in order to prevent the consequences of hypoxia or hyperoxia.

Fetal oxygen and glucose utilization of uncomplicated monochorionic twins: Adapting to the intrauterine environment

IntroductionMonochorionic twins (MC) develop under unique intrauterine conditions and show a high risk of compromise during fetal life. Here we describe umbilical vein blood flow (UVBF) and fetal oxygen and glucose utilization in uncomplicated MC twins and investigate possible differences within twin-pairs according to birth-order. MethodsProspective single-center study on 48 uncomplicated MC twins enrolled at the time of elective cesarean delivery. Ultrasound measurements of UVBF for Twin 1 and Twin 2 labelled according to birth-order were performed before spinal anesthesia. Umbilical arterial and venous blood samples were collected for each twin after fetal delivery, and fetal oxygen and glucose deliveries and uptakes were computed. ResultsAll twins were delivered within 2 min from one-another under steady-state conditions at 36.4 weeks of median gestational age (IQR 36.0–37.0). Birthweight and umbilical cord gas analyses were within physiological ranges for all twins. Second-born twins showed significantly lower UVBF, measured before delivery, and lower median birthweight compared to first-borns. Moreover, median values of estimated fetal oxygen and glucose consumption were lower in second compared to first MC twins. DiscussionUncomplicated MC twins show different birthweight, oxygenation and metabolic rates based on their position in utero, hinting at pre-existing conditions possibly deriving by uneven vascular and metabolic distribution of the two placental territories. The innovative findings of this study emphasize the biological uniqueness of these pregnancies and prompt further physiological studies on MC twins and placenta metabolism.

Cross-Sectional Observational Study of Typical in utero Fetal Movements Using Machine Learning

Early variations of fetal movements are the hallmark of a healthy developing central nervous system. However, there are no automatic methods to quantify the complex 3D motion of the developing fetus in utero. The aim of this prospective study was to use machine learning (ML) on in utero MRI to perform quantitative kinematic analysis of fetal limb movement, assessing the impact of maternal, placental, and fetal factors. In this cross-sectional, observational study, we used 76 sets of fetal (24–40 gestational weeks [GW]) blood oxygenation level-dependent (BOLD) MRI scans of 52 women (18–45 years old) during typical pregnancies. Pregnant women were scanned for 5–10 min while breathing room air (21% O₂) and for 5–10 min while breathing 100% FiO₂ in supine and/or lateral position. BOLD acquisition time was 20 min in total with effective temporal resolution approximately 3 s. To quantify upper and lower limb kinematics, we used a 3D convolutional neural network previously trained to track fetal key points (wrists, elbows, shoulders, ankles, knees, hips) on similar BOLD time series. Tracking was visually assessed, errors were manually corrected, and the absolute movement time (AMT) for each joint was calculated. To identify variables that had a significant association with AMT, we constructed a mixed-model ANOVA with interaction terms. Fetuses showed significantly longer duration of limb movements during maternal hyperoxia. We also found a significant centrifugal increase of AMT across limbs and significantly longer AMT of upper extremities <31 GW and longer AMT of lower extremities >35 GW. In conclusion, using ML we successfully quantified complex 3D fetal limb motion in utero and across gestation, showing maternal factors (hyperoxia) and fetal factors (gestational age, joint) that impact movement. Quantification of fetal motion on MRI is a potential new biomarker of fetal health and neuromuscular development.

T2* weighted fetal MRI and the correlation with placental dysfunction

IntroductionTransverse relaxation time (T2*) is related to tissue oxygenation and morphology. We aimed to describe T2* weighted MRI in selected fetal organs in normal pregnancies, and to investigate the correlation between fetal organ T2* and placental T2*, birthweight (BW) deviation, and redistribution of fetal blood flow. MethodsT2*-weighted MRI was performed in 126 singleton pregnancies between 23+6- and 41+3-weeks’ gestation. The T2* value was obtained from the placenta and fetal organs (brain, lungs, heart, liver, kidneys, and spleen). In normal BW pregnancies (BW > 10th centile), the correlation between the T2* value and gestational age (GA) at MRI was estimated by linear regression. The correlation between fetal organ Z-score and BW group was demonstrated by boxplots and investigated by analysis of variance (ANOVA) for each organ. ResultsIn normal BW pregnancies fetal organ T2* was negatively correlated with GA. We found a significant correlation between BW group and fetal organ T2* z-score in the fetal heart, kidney, lung and spleen. A positive linear correlation was demonstrated between fetal organ T2* and outcomes related to placental function such as BW deviation and placenta T2* in all investigated fetal organs except for the fetal liver. In the fetal heart, kidneys, and spleen the T2* value showed a significant correlation with fetal redistribution of blood flow (Middle cerebral artery Pulsatility Index) before delivery. DiscussionFetal T2* is correlated with BW, placental function, and redistribution of fetal blood flow, suggesting that fetal organ T2* reflects fetal oxygenation and morphological changes related to placental dysfunction.

Chronic prenatal delta-9-tetrahydrocannabinol exposure adversely impacts placental function and development in a rhesus macaque model

Cannabis use in pregnancy is associated with adverse perinatal outcomes, which are likely mediated by the placenta. However, the underlying mechanisms and specific vasoactive effects of cannabis on the placenta are unknown. Our objective was to determine the impact of chronic prenatal delta-tetrahydrocannabinol (THC, main psychoactive component of cannabis) exposure on placental function and development in a rhesus macaque model using advanced imaging. Animals were divided into two groups, control (CON, n = 5) and THC-exposed (THC, n = 5). THC-exposed animals received a THC edible daily pre-conception and throughout pregnancy. Animals underwent serial ultrasound and MRI at gestational days 85 (G85), G110, G135 and G155 (full term is ~ G168). Animals underwent cesarean delivery and placental collection at G155 for histologic and RNA-Seq analysis. THC-exposed pregnancies had significantly decreased amniotic fluid volume (p < 0.001), placental perfusion (p < 0.05), and fetal oxygen availability (p < 0.05), all indicators of placental insufficiency. Placental histological analysis demonstrated evidence of ischemic injury with microinfarctions present in THC-exposed animals only. Bulk RNA-seq demonstrated that THC alters the placental transcriptome and pathway analysis suggests dysregulated vasculature development and angiogenesis pathways. The longer-term consequences of these adverse placental findings are unknown, but they suggest that use of THC during pregnancy may deleteriously impact offspring development.

Nudo verdadero como causa de taquicardia fetal persistente. Reporte de un caso

Umbilical cord abnormalities are associated with adverse effects during pregnancy. The true umbilical cord knot is present in 0.3-2.1% of pregnancies and has been associated with fetal death. Risk factors include maternal age, high BMI, multiparity, hypertensive disorders, smoking, polyhydramnios, gestational diabetes, male sex of the fetus, and other malformations. Prenatal diagnosis of the true knot is rare and challenging. Most are diagnosed at birth and only 0.08% of true knots are diagnosed prenatally. Non-reassuring cardiotocography traces may be present, reflecting hypoxic or mechanical stress disrupting fetal oxygenation. The aim of this case report is to present a case of true umbilical cord knot presenting with persistent fetal tachycardia during labor, resolved by vaginal delivery. Keywords: True knot; umbilical cord; fetal achycardia; stillbirth; fetal asphyxia.

Association between maternal oxygenation and brain growth in fetuses with left-sided cardiac obstructive lesions.

Impaired brain growth has been observed in fetuses with left-sided obstructive lesions (LSOL). Maternal oxygenation (MO) can alter fetal cerebral oxygenation and vascular reactivity. Our aim was to observe whether brain growth improves during MO in fetuses with LSOL. Forty-six fetuses with LSOL and 23 control fetuses were enrolled in this prospective longitudinal study. Fetuses with LSOL were subgrouped into those with MO (LSOL-MO, n = 23) and those without MO (LSOL-nMO, n = 23). Fetal head circumference (HC) and total intracranial volume (TIV) were evaluated serially at 4-week intervals. Brain biometry and growth were analyzed using linear mixed models adjusted for gestational age and sex. Spearman's correlation coefficients were calculated to identify baseline characteristics predictive of brain growth in the LSOL-MO group. Duration of MO therapy had significant interaction effects on cerebral biometry in fetuses with LSOL. TIV increased more rapidly after 8 weeks of oxygen exposure and HC was larger after 16 weeks of oxygen exposure in the LSOL-MO group compared with the LSOL-nMO group (P &lt; 0.001). The change in TIV at the final time- point relative to the initial timepoint in the LSOL-MO group correlated negatively with the baseline pulsatility index of the middle cerebral artery (r = -0.58, P = 0.003) and baseline myocardial performance index of the left ventricle (r = -0.68, P &lt; 0.001). TIV and HC increased faster in fetuses with LSOL which had MO compared with those that did not. Lower cerebral vascular resistance and preserved left heart function at baseline may predict greater cerebral biometric growth during MO. Additional research, including larger serial studies, is needed to confirm these preliminary findings and evaluate the clinical application of MO in this population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Placental MRI Predicts Fetal Oxygenation and Growth Rates in Sheep and Human Pregnancy.

Magnetic resonance imaging (MRI) assessment of fetal blood oxygen saturation (SO2) can transform the clinical management of high‐risk pregnancies affected by fetal growth restriction (FGR). Here, a novel MRI method assesses the feasibility of identifying normally grown and FGR fetuses in sheep and is then applied to humans. MRI scans are performed in pregnant ewes at 110 and 140 days (term = 150d) gestation and in pregnant women at 28+3 ± 2+5 weeks to measure feto‐placental SO2. Birth weight is collected and, in sheep, fetal blood SO2 is measured with a blood gas analyzer (BGA). Fetal arterial SO2 measured by BGA predicts fetal birth weight in sheep and distinguishes between fetuses that are normally grown, small for gestational age, and FGR. MRI feto‐placental SO2 in late gestation is related to fetal blood SO2 measured by BGA and body weight. In sheep, MRI feto‐placental SO2 in mid‐gestation is related to fetal SO2 later in gestation. MRI feto‐placental SO2 distinguishes between normally grown and FGR fetuses, as well as distinguishing FGR fetuses with and without normal Doppler in humans. Thus, a multi‐compartment placental MRI model detects low placental SO2 and distinguishes between small hypoxemic fetuses and normally grown fetuses.

Fetal growth restriction and stillbirth: Biomarkers for identifying at risk fetuses.

Fetal growth restriction (FGR) is a major cause of stillbirth, prematurity and impaired neurodevelopment. Its etiology is multifactorial, but many cases are related to impaired placental development and dysfunction, with reduced nutrient and oxygen supply. The fetus has a remarkable ability to respond to hypoxic challenges and mounts protective adaptations to match growth to reduced nutrient availability. However, with progressive placental dysfunction, chronic hypoxia may progress to a level where fetus can no longer adapt, or there may be superimposed acute hypoxic events. Improving detection and effective monitoring of progression is critical for the management of complicated pregnancies to balance the risk of worsening fetal oxygen deprivation in utero, against the consequences of iatrogenic preterm birth. Current surveillance modalities include frequent fetal Doppler ultrasound, and fetal heart rate monitoring. However, nearly half of FGR cases are not detected in utero, and conventional surveillance does not prevent a high proportion of stillbirths. We review diagnostic challenges and limitations in current screening and monitoring practices and discuss potential ways to better identify FGR, and, critically, to identify the “tipping point” when a chronically hypoxic fetus is at risk of progressive acidosis and stillbirth.

Quality of fetal heart rate monitoring with transabdominal fetal ECG during maternal movement in labor: A prospective study.

Transabdominal electrocardiographic (TAfECG) acquisition of fetal heart rate (FHR) signals has recently been introduced into leading commercial cardiotocographic (CTG) monitors. Continuous wireless transmission of signals has raised the possibility of the technology being used during maternal mobilization in labor. This study aims to evaluate signal quality and accuracy of TAfECG acquisition of FHR signals during static and active maternal positions in labor when compared with Doppler signals and with the gold-standard method of fetal scalp electrode (FSE). A total of 76 women with singleton term pregnancies in the active first stage of labor had simultaneously acquired FHR with TAfECG, Doppler, and FSE. Participants were asked to complete a supervised mobilization scheme, comprising five sequential 10-min periods of lying down, standing, sitting, walking, and rocking on the birthing ball. The three FHR signals were compared, defining signal loss as the percentage of signals under 20 bpm or exceeding 250 bpm and accuracy as the difference with FSE values. Computer analysis was used to quantify variability, accelerations, and decelerations. Static labor positions (lying down, standing, and sitting) were compared with active labor positions (walking and rocking on the birthing ball). Average signal loss was 5.3% with TAfECG (3.2% in static and 7.4% in active positions) and 15.5% with Doppler (8.3% in static and 30.7% in active positions). Average accuracy was 3.5bpm with TAfECG (1.9bpm in static and 5.04 bpm in active positions) and 13.9bpm with Doppler (3.2bpm in static and 24.7bpm in active positions). Average variability was similar with TAfECG and FSE in static positions but significantly higher with TAfECG in active positions (23.6 vs. 13.5 bpm, p < 0.001). In static labor positions, TAfECG provides a low signal loss, similar to that obtained with FSE, and a good signal accuracy, so the technique can be considered reliable when the mother is lying down, standing, or sitting. During maternal movement, TAfECG causes an artificial increase in FHR variability, which can cause false reassurance regarding fetal oxygenation. Doppler signals are unreliable during maternal movements.

Fetoplacental oxygen homeostasis in pregnancies with maternal diabetes mellitus and obesity.

Despite improvements in clinical management, pregnancies complicated by pre-existing diabetes mellitus, gestational diabetes mellitus or obesity carry substantial risks for parent and offspring. Some of the endocrine and metabolic changes in parent and fetus in diabetes mellitus and obesity lead to fetal oxygen deficit, mostly due to insulin-induced accelerated fetal metabolism. The human fetus deals with reduced oxygenation through a wide range of adaptive responses that act at various levels in the placenta as well as the fetus. These responses ensure adequate oxygen delivery to the fetus, increase the oxygen transport capacity of fetal blood and redistribute oxygen-rich blood to vital organs such as the brain and heart. The liver has a central role in adapting to reduced oxygenation by increasing its oxygen extraction and stimulating erythropoietin synthesis to increase haematocrit. The type of adaptive response depends on the onset and duration of hypoxia and the severity of the metabolic disturbance. In pregnancies characterized by diabetes mellitus or obesity, these adaptive systems come under additional strain owing to the increased maternal supply of glucose and resultant fetal hyperinsulinaemia, both of which stimulate oxidative metabolism. In the rare situation that the adaptive responses are overwhelmed, stillbirth can ensue.

Fetal Hemoglobin and Cerebral Tissue Oxygenation during Immediate Postnatal Transition

Introduction: Concentration of fetal hemoglobin (HbFc) in human neonates determines oxygen-carrying capacity of blood and the position of oxyhemoglobin dissociation curve. Near-infrared spectroscopy enables the measurement of regional cerebral tissue oxygen saturation (rScO2) and in combination with measurements of pulsatile arterial oxygen saturation (SpO2), the calculation of cerebral fractional tissue oxygen extraction (cFTOE). Methods: We aimed to investigate the impact of HbFc on rScO2, cFTOE, and SpO2 in preterm and term neonates during the first 15 min after birth. Blood analyses provided total blood hemoglobin (Hb) and HbFc measurements. Correlations between HbFc, Hb and rScO2, cFTOE, and SpO2 in each minute were analyzed. Results: Ninety term and 19 preterm neonates without medical support were included. HbFc was significantly higher in preterm neonates, whereas there were no significant differences in Hb between the groups. In preterm neonates, we found positive correlations of both HbFc and Hb with rScO2 and negative correlations of HbFc and Hb with cFTOE in the first minutes after birth. In contrast, there were no significant correlations between the same parameters in term neonates. Correlations between HbFc or Hb and SpO2 were either insignificant, negligible, or very low in both groups. Discussion/Conclusion: In preterm neonates, higher HbFc was associated with higher rScO2 and lower cFTOE in the first minutes after birth. This phenomenon could not be confirmed in term neonates and might reflect immature autoregulation of oxygen delivery to the brain or lower oxygen consumption in preterm neonates in the first minutes of immediate postnatal transition.

Systemic Maternal Human sFLT1 Overexpression Leads to an Impaired Foetal Brain Development of Growth-Restricted Foetuses upon Experimental Preeclampsia.

The pregnancy disorder preeclampsia (PE) is characterized by maternal hypertension, increased level of circulating antiangiogenic soluble fms-like tyrosine kinase-1 (sFLT1), and reduced placental perfusion, leading to foetal growth restriction (FGR) and preterm birth. All these adverse effects are associated with neurocognitive disorders in the offspring. However, the direct interplay between increased antiangiogenesis during PE and disturbed foetal brain development independent of prematurity has not been investigated yet. To examine foetal brain development in sFLT1-related PE, hsFLT1/rtTA-transgenic mice with systemic (maternal or maternal/fetoplacental) human sFLT1 (hsFLT1) overexpression since 10.5 days postconception (dpc) were used, and histological and molecular analyses of foetal brains were performed at 18.5 dpc. Consequences of elevated hsFLT1 on placental/foetal vascularization and hypoxia of placentas and foetal brains were analysed using the hypoxia markers pimonidazole and hemeoxygenase-1 (HO-1). Immunohistochemical analysis revealed increased hypoxia in placentas of PE-affected pregnancies. Moreover, an increase in HO-1 expression was observed upon elevated hsFLT1 in placentas and foetal brains. PE foetuses revealed asymmetrical FGR by increased brain/liver weight ratio. The brain volume was reduced combined with a reduction in the cortical/hippocampal area and an increase of the caudate putamen and its neuroepithelium, which was associated with a reduced cell density in the cortex and increased cell density in the caudate putamen upon hsFLT1 overexpression. Mild influences were observed on brain vasculature shown by free iron deposits and mRNA changes in Vegf signalling. Of note, both types of systemic hsFLT1 overexpression (indirect: maternal or direct: maternal/fetoplacental) revealed similar changes with increasing severity of impaired foetal brain development. Overall, circulating hsFLT1 in PE pregnancies impaired uteroplacental perfusion leading to disturbed foetal oxygenation and brain injury. This might be associated with a disturbed cell migration from the caudate putamen neuroepithelium to the cortex which could be due to disturbed cerebrovascular adaption.

Effect of Different Positions During Surgical Preparation With Combined Spinal-Epidural Anesthesia for Elective Cesarean Delivery: A Randomized Controlled Trial

(Anesth Analg. 2021;133:1235–1243) A lateral tilt of the uterus is used to reduce pressure on the inferior vena cava in pregnant patients undergoing cesarean delivery. This may improve the fetal blood and oxygen supply. This position has been thought to improve the fetal acid-base status, though this has been recently called into question. This study aimed to evaluate whether moving the patient into a 30 degrees left lateral tilt position before elective cesarean delivery with combined spinal-epidural anesthesia could better improve the fetal acid-base status compared with a 15 degrees left lateral tilt or supine position.

Histopathological features in advanced abdominal pregnancies co-infected with SARS-CoV-2 and HIV-1 infections: A case evaluation.

ObjectivesThis study aims to provide a semi-qualitative histopathological report of the dual SARS-CoV-2 and HIV infected placentae in the third trimester of Advanced Abdominal Pregnancy (AAP).Study designFour AAP placentae in the third trimester of pregnancy (two positive for HIV-1 and two positives for SARS-CoV-2) were histologically examined.ResultsThe SARS-CoV-2+ HIV+ placentae were dysmorphic in shape compared to the flattened disc-like shape noted in the SARS-CoV-2+HIV-, SARS-CoV-2-HIV+and SARS-CoV-2-HIV- placentae. Diffused syncytial knots and syncytial degeneration were observed in all placentae. Intermittent cytotrophoblast increase, perivillous and intravillous fibrin deposition, mononuclear inflammatory cells with widespread degeneration/necrosis of the syncytiotrophoblast and microcalcification were pronounced in the SARS-CoV-2+HIV+ compared to the SARS-CoV-2+HIV- placentae. Vascular pathological changes included thrombi, ectasis, mural hypertrophy and atherotic vessels.ConclusionElevated syncytial trophoblast injury, villitis, microcalcifications and mineralisation of the syncytial basement membrane in the AAP placentae may be due to SARS-CoV-2 viral transgression instead of HIV infection alone. Vascular malperfusion is suggestive of a hypoxic insult arising from a compensatory response to meet the fetal oxygen and nutrient demands of an AAP. Placentae from HIV infected women on antiretroviral treatment were characterised by vascular malperfusion.

Prenatal Oxygen and Glucose Therapy Normalizes Insulin Secretion and Action in Growth-Restricted Fetal Sheep.

Placental insufficiency (PI) lowers fetal oxygen and glucose concentrations, which disrupts glucose-insulin homeostasis and promotes fetal growth restriction (FGR). To date, prenatal treatments for FGR have not attempted to correct the oxygen and glucose supply simultaneously. Therefore, we investigated whether a 5-day correction of oxygen and glucose concentrations in PI-FGR fetuses would normalize insulin secretion and glucose metabolism. Experiments were performed in near-term FGR fetal sheep with maternal hyperthermia-induced PI. Fetal arterial oxygen tension was increased to normal levels by increasing the maternal inspired oxygen fraction and glucose was infused into FGR fetuses (FGR-OG). FGR-OG fetuses were compared with maternal air insufflated, saline-infused fetuses (FGR-AS) and control fetuses. Prior to treatment, FGR fetuses were hypoxemic and hypoglycemic and had reduced glucose-stimulated insulin secretion (GSIS). During treatment, oxygen, glucose, and insulin concentrations increased, and norepinephrine concentrations decreased in FGR-OG fetuses, whereas FGR-AS fetuses were unaffected. On treatment day 4, glucose fluxes were measured with euglycemic and hyperinsulinemic-euglycemic clamps. During both clamps, rates of glucose utilization and production were greater in FGR-AS than FGR-OG fetuses, while glucose fluxes in FGR-OG fetuses were not different than control rates. After 5 days of treatment, GSIS increased in FGR-OG fetuses to control levels and their ex vivo islet GSIS was greater than FGR-AS islets. Despite normalization in fetal characteristics, GSIS, and glucose fluxes, FGR-OG and FGR-AS fetuses weighed less than controls. These findings show that sustained, simultaneous correction of oxygen and glucose normalized GSIS and whole-body glucose fluxes in PI-FGR fetuses after the onset of FGR.

Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism†.

Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal hepatic development. We also determined whether paternal obesity indirectly affects the in utero environment by disrupting maternal metabolic adaptations to pregnancy. Male mice fed a standard chow or high fat diet (60%kcal fat) for 8–10 weeks were time-mated with female mice to generate pregnancies and offspring. Glucose tolerance was evaluated in dams at mid-gestation (embryonic day (E) 14.5) and late gestation (E18.5). Hypoxia, angiogenesis, endocrine function, macronutrient transport, and ER stress markers were evaluated in E14.5 and E18.5 placentae and/or fetal livers. Maternal glucose tolerance was assessed at E14.5 and E18.5. Metabolic parameters were assessed in offspring at ~60 days of age. Paternal obesity did not alter maternal glucose tolerance but induced placental hypoxia and altered placental angiogenic markers, with the most pronounced effects in female placentae. Paternal obesity increased ER stress-related protein levels (ATF6 and PERK) in the fetal liver and altered hepatic expression of gluconeogenic factors at E18.5. Offspring of obese fathers were glucose intolerant and had impaired whole-body energy metabolism, with more pronounced effects in female offspring. Metabolic deficits in offspring due to paternal obesity may be mediated by sex-specific changes in placental vessel structure and integrity that contribute to placental hypoxia and may lead to poor fetal oxygenation and impairments in fetal metabolic signaling pathways in the liver.

A174 PERCEPTIONS OF CANNABIS USE IN WOMEN WITH INFLAMMATORY BOWEL DISEASE OF REPRODUCTIVE AGE: A CROSS-SECTIONAL STUDY

BackgroundCannabis use in inflammatory bowel disease (IBD) may lead to improvement in pain and general health perception. However, its use during pregnancy may result in adverse outcomes such as preterm birth and altered fetal brain development. It remains unknown how women with IBD perceive Cannabis use during pregnancy and whether they discuss its use with their health-care providers.AimsTo determine practices in, and perceptions of, cannabis use during pregnancy in women with IBD of reproductive age.MethodsWomen with IBD (age 18–45) were recruited at Mount Sinai Hospital and via social media platforms. Participants anonymously completed surveys on baseline demographics and IBD characteristics. They also completed a Cannabis questionnaire which asked about current use, perceived risks during pregnancy, and discussions with health-care providers. Categorical variables were reported as frequencies and compared using the chi-square test. Continuous variables were reported as medians and compared using the Mann-Whitney U test.ResultsSixty-four women were included, 26 (40.6%) with ulcerative colitis, 37 (57.8%) with Crohn’s disease, and 1 (1.6%) with indeterminate colitis. Nineteen (29.7%) were preconception, 40 (62.5%) were pregnant, and 5 (7.8%) were post-partum. Eleven (18.0%) patients reported current Cannabis use, 4 (6.3%) during pregnancy. Cannabis users were more likely to have discussed its use with a health-care provider compared to non-users (45.5% vs. 5.7%, p<0.001) and had longer IBD duration (12.00 vs. 9.00 years, p=0.05). Twenty-five (42.4%) were unsure of the risks of Cannabis use in pregnancy, of which only two had discussed this with a health-care provider. Reasons for fear of Cannabis use included risk of fetal oxygen restriction (n=13, 20.3%), impact on brain development (n=29, 46.0%), and risk of fetal respiratory issues (n=18, 28.6%). Only eight (12.5%) patients reported having a conversation about Cannabis use during pregnancy with their health-care provider; all of whom felt its consumption was unsafe during pregnancy.ConclusionsMany women with IBD report being unsure of risks of Cannabis use during pregnancy. With the legalization of Cannabis in Canada, it is imperative patients and health-care providers discuss the risks and benefits of its use, particularly during vulnerable times such as pregnancy.Funding AgenciesNone

Extracorporeal Membrane Oxygenation for Pregnant and Postpartum Patients.

Extracorporeal membrane oxygenation (ECMO) has seen increasing use for critically ill pregnant and postpartum patients over the past decade. Growing experience continues to demonstrate the feasibility of ECMO in obstetric patients and attest to its favorable outcomes. However, the interaction of pregnancy physiology with ECMO life support requires careful planning and adaptation for success. Additionally, the maintenance of fetal oxygenation and perfusion is essential for safely continuing pregnancy during ECMO support. This review summarizes the considerations for use of ECMO in obstetric patients and how to address these concerns.