Fetal heart rate evolution patterns in cerebral palsy associated with umbilical cord complications: a nationwide study.

BACKGROUND: The aim of the present study was to clarify fetal heart rate (FHR) evolution patterns in infants with cerebral palsy (CP) according to different types of umbilical cord complications. METHODS: This case-control study included children born: with a birth weight ≥2000 g, at gestational age ≥33 weeks, with disability due to CP, and between 2009 and 2014. Obstetric characteristics and FHR patterns were compared among patients with CP associated with (126 cases) and without (594 controls) umbilical cord complications. RESULTS: There were 32 umbilical cord prolapse cases and 94 cases with coexistent antenatal umbilical cord complications. Compared with the control group, the persistent non-reassuring pattern was more frequent in cases with coexistent antenatal umbilical cord complications (p = 0.012). A reassuring FHR pattern was observed on admission, but resulted in prolonged deceleration, especially during the first stage of labor, and was significantly identified in 69% of cases with umbilical cord prolapse and 35% of cases with antenatal cord complications, compared to 17% of control cases (p < 0.001). CONCLUSION: Hypercoiled cord and abnormal placental umbilical cord insertion, may be associated with CP due to acute hypoxic-ischemic injury as well as sub-acute or chronic adverse events during pregnancy, while umbilical cord prolapse may be characterized by acute hypoxic-ischemic injury during delivery.

Common pathogenesis for sirenomelia, OEIS complex, limb-body wall defect, and other malformations of caudal structures.

Decades of clinical, pathological, and epidemiological study and the recent application of advanced microarray and gene sequencing technologies have led to an understanding of the causes and pathogenesis of most recognized patterns of malformation. Still, there remain a number of patterns of malformation whose pathogenesis has not been established. Six such patterns of malformation are sirenomelia, VACTERL association, OEIS complex, limb-body wall defect (LBWD), urorectal septum malformation (URSM) sequence, and MURCS association, all of which predominantly affect caudal structures. On the basis of the overlap of the component malformations, the co-occurrence in individual fetuses, and the findings on fetal examination, a common pathogenesis is proposed for these patterns of malformation. The presence of a single artery in the umbilical cord provides a visible clue to the pathogenesis of all cases of sirenomelia and 30%-50% of cases of VACTERL association, OEIS complex, URSM sequence, and LBWD. The single artery is formed by a coalescence of arteries that supply the yolk sac, arises from the descending aorta high in the abdominal cavity, and redirects blood flow from the developing caudal structures of the embryo to the placenta. This phenomenon during embryogenesis is termed vitelline vascular steal.

Regeneration in Experimental Alveolar Bone Defect Using Human Umbilical Cord Mesenchymal Stem Cells.

Cleft lip and palate is a congenital disorder including cleft lip, and/or cleft palate, and/or alveolar cleft, with high incidence.The alveolar cleft causes morphological and functional abnormalities. To obtain bone bridge formation and continuous structure between alveolar clefts, surgical interventions are performed from infancy to childhood. However, desirable bone bridge formation is not obtained in many cases. Regenerative medicine using mesenchymal stem cells (MSCs) is expected to be a useful strategy to obtain sufficient bone bridge formation between alveolar clefts. In this study, we examined the effect of human umbilical cord-derived MSCs by transplantation into a rat experimental alveolar cleft model. Human umbilical cords were digested enzymatically and the isolated cells were collected (UC-EZ cells). Next, CD146-positive cells were enriched from UC-EZ cells by magnetic-activated cell sorting (UC-MACS cells). UC-EZ and UC-MACS cells showed MSC gene/protein expression, in vitro. Both cells had multipotency and could differentiate to osteogenic, chondrogenic, and adipogenic lineages under the differentiation-inducing media. However, UC-EZ cells lacked Sox2 expression and showed the lower ratio of MSCs than UC-MACS cells. Thus, UC-MACS cells were transplanted with hydroxyapatite and collagen (HA + Col) into alveolar cleft model to evaluate bone formation in vivo. The results of micro computed tomography and histological staining showed that UC-MACS cells with HA + Col induced more abundant bone formation between the experimental alveolar clefts than HA + Col implantation only. Cells immunopositive for osteopontin were accumulated along the bone surface and some of them were embedded in the bone. Cells immunopositive for human-specific mitochondria were aligned along the newly formed bone surface and in the new bone, suggesting that UC-MACS cells contributed to the bone bridge formation between alveolar clefts. These findings indicate that human umbilical cords are reliable bioresource and UC-MACS cells are useful for the alveolar cleft regeneration.

The effect of nuchal umbilical cord on fetal cardiac and cerebral circulation-cross-sectional study.

OBJECTIVES: The subject of our analysis is the influence of umbilical cord collision around the fetal neck on the fetal heart function and cerebral circulation. METHODS: Our study was carried out on a group of 115 fetuses from single pregnancies with physiological course, during the 15th to 40th week of pregnancy. In our analysis, we examined the following parameters: Tei index for right ventricle, Tei index for left ventricle with Tei index components: isovolumetric contraction time, isovolumetric relaxation time, ejection time and cardiothoracic area ratio, middle cerebral artery peak systolic velocity (PS MCA), middle cerebral artery pulsatility index (PI MCA). Gestational age in our study was: 28+2±34. The study group of patients with fetal umbilical cord around neck group (fUCAN) included 38 fetuses (20 males, 18 females). The control group of patients with no fetal umbilical cord around neck group (NfUCAN) included 77 fetuses (43 males, 34 females). RESULTS: In our study, we found no significant differences in the values obtained: Tei LV in fUCAN: 0.5±0.1 vs. in NfUCAN: 0.5±0.1; p=0.42), Tei RV in fUCAN: 0.5±0.2 vs. in NfUCAN: 0.4±0.1; (p=0.2). Tricuspid valve regurgitation-TR was observed with the following frequency: fUCAN: 7/38, 18% vs. NfUCAN: 13/77, 17%; p=0.8. MCA PS in study fUCAN group was significantly higher than in NfUCAN (40.2±11.5 vs. 32.5±9.5; p=0.003), although other hemodynamic and clinical variables did not differ between the study and control groups. CONCLUSIONS: The fetal nuchal umbilical cord collision did not affect the fetal heart function expressed as Tei index, at the time of fetal heart examination (at mean gestational age 29+4 weeks). The fUCAN group presented elevated PS MCA, which was not related to other hemodynamic and clinical variables between the study and control groups.

Short-term efficacy of umbilical cord milking in preterm infants: systematic review and meta-analysis.

BACKGROUND: To systematically evaluate short-term efficacy of UCM versus other interventions in preterm infants. METHODS: Six engines were searched until February 2020 for randomized controlled trials (RCTs) assessing UCM versus immediate cord clamping (ICC), delayed cord clamping (DCC), or no intervention. Primary outcomes were overall mortality, intraventricular hemorrhage (IVH), and patent ductus arteriosus (PDA); secondary outcomes were need for blood transfusion, mean blood pressure (MBP), serum hemoglobin (Hb), and ferritin levels. Random-effects meta-analyses were used. RESULTS: Fourteen RCTs (n = 1708) were included. In comparison to ICC, UCM did not decrease mortality (RR 0.5, 95% CI 0.2-1.1), IVH (RR 0.7, 95% CI 0.5-1.0), or PDA (RR 1.0, 95% CI 0.7-1.5). However, UCM reduced need of blood transfusion (RR 0.5, 95% CI 0.3-0.9) and increased MBP (MD 2.5 mm Hg, 95% CI 0.5-4.5), Hb (MD 1.2 g/dL, 95% CI 0.8-1.6), and ferritin (MD 151.4 ng/dL, 95% CI 59.5-243.3). In comparison to DCC, UCM did not reduce mortality, IVH, PDA, or need of blood transfusion but increased MBP (MD 3.7, 95% CI 0.6-6.9) and Hb (MD 0.3, 95% CI -0.2-0.8). Only two RCTs had high risk of bias. CONCLUSIONS: UCM did not decrease short-term clinical outcomes in comparison to ICC or DCC in preterm infants. Intermediate outcomes improved significantly with UCM. IMPACT: In 14 randomized controlled trials (RCTs), umbilical cord milking (UCM) did not reduce mortality, intraventricular hemorrhage, or patent ductus arteriosus compared to immediate (ICC) or delayed cord clamping (DCC). UCM improved mean blood pressure and hemoglobin levels compared to ICC or DCC. In comparison to ICC, UCM reduced the need for blood transfusion. We updated searches until February 2020, stratified by type of control, and performed subgroup analyses. There was low quality of evidence about clinical efficacy of UCM. Most of RCTs had low risk of bias. UCM cannot be recommended as standard of care for preterm infants.

Fetal Vascular Malperfusion Due To Long and Hypercoiled Umbilical Cords Resulting in Recurrent Second Trimester Pregnancy Loss: A Case Series and Literature Review.

BACKGROUND: Intrauterine fetal demise due to fetal vascular malperfusion in mid-gestation is a rare occurrence. Abnormally long and hypercoiled umbilical cords are associated with an increased risk of umbilical cord blood flow restriction, which in turn can result in adverse perinatal and maternal outcomes. The factors that regulate umbilical cord development, specifically umbilical cord length and coiling, are poorly understood. METHODS: Maternal history, along with fetal and placental findings (post-mortem, pathological, and molecular), were reviewed for a series of 3 consecutive pregnancies that ended in second trimester intrauterine fetal demise. RESULTS: All 3 umbilical cords were exceptionally long and hypercoiled, and all placentas showed evidence of high-grade fetal vascular malperfusion. At fetopsy, all 3 fetuses were developmentally normal for gestational age and lacked congenital anomalies. Maternal medical history and antenatal testing (including an extensive work-up for maternal hypercoagulability syndromes) were normal and/or noncontributory. CONCLUSION: Although excessively long and hypercoiled cords are generally thought of as sporadic, nongenetic events, rare examples of recurrent intrauterine fetal demise secondary to such exist have been reported. This intrafamilial clustering of a rare event is suggestive that at least a subset of hypercoiled, long umbilical cords may have an underlying genetic etiology.

Umbilical Cord Prolapse: A Review of the Literature.

IMPORTANCE: Umbilical cord prolapse is a rare occurrence and is a life-threatening emergency for the fetus. These events are unpredictable and unpreventable. Umbilical cord prolapse requires swift diagnosis and management for optimal outcome. OBJECTIVE: The aim of this review is to describe the incidence, risk factor, pathophysiology, diagnosis, and management of this rare but potentially life-threatening event. EVIDENCE ACQUISITION: A PubMed, Web of Science, and CINAHL search was undertaken with no limitations on the number of years searched. RESULTS: There were 200 articles identified, with 53 being the basis of review. Multiple risk factors for a umbilical cord prolapse have been suggested including fetal malpresentation or abnormal lie, prematurity, multifetal gestation, and polyhydramnios. The diagnosis is largely made by examination and found after rupture of membranes, and most often, examination is prompted by fetal heart rate decelerations. The management of umbilical cord prolapse is expedited delivery; however, there are rare specific scenarios in which immediate delivery is not possible and efforts should be made to relieve cord compression. CONCLUSIONS: Rapid identification of an umbilical cord prolapse facilitates management and increases likelihood of an optimal outcome. The management is an expedited delivery with efforts to relieve cord compression until delivery can be achieved. RELEVANCE: Umbilical cord prolapse is a rare but a life-threatening obstetrical emergency.

Effects of the Insulted Neuronal Cells-Derived Extracellular Vesicles on the Survival of Umbilical Cord-Derived Mesenchymal Stem Cells following Cerebral Ischemia/Reperfusion Injury.

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) engraftment is a potential therapy for cerebral ischemic stroke. However, the harsh microenvironment induced by cerebral ischemia/reperfusion restricts the survival rate and therapeutic efficiency of the engrafted UC-MSCs. In this study, we explored whether small extracellular vesicles (EVs) derived from injured neuronal cells following exposure to cerebral ischemia/reperfusion insult affect the survival of transplanted UC-MSCs. To establish a simulation of cerebral ischemia/reperfusion microenvironment comprising engrafted UC-MSCs and neuronal cells, we cocultured EVs derived from injured N2A cells, caused by exposure to oxygen-glucose deprivation and reperfusion (OGD/R) insult, with UC-MSCs in a conditioned medium. Coculture of UC-MSCs with EVs exacerbated the OGD/R-induced apoptosis and oxidative stress. Suppression of EVs-release via knock-down of Rab27a effectively protected the UC-MSCs from OGD/R-induced insult. Moreover, hypoxia preconditioning not only elevated the survival of UC-MSCs but also improved the paracrine mechanism of injured N2A cells. Altogether, these results show that EVs from injured N2A cells exacerbates OGD/R-induced injury on transplanted UC-MSCs in vitro. Hypoxia preconditioning enhances the survival of the engrafted-UC-MSCs; hence, thus could be an effective approach for improving UC-MSCs therapy in ischemic stroke.

Intermittent absent and reversed umbilical artery flows in appropriately grown monochorionic diamniotic twins in relation to proximate cord insertion: A harmful combination?

OBJECTIVE: To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome. METHODS: The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated. RESULTS: iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress. CONCLUSION: iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.

Bioinformatics enrichment analysis of genes and pathways related to maternal type 1 diabetes associated with adverse fetal outcomes.

Maternal type 1 diabetes mellitus (T1DM) may affect fetal development by altering the gene expression profile of the umbilical cord. The present study aimed to explore the T1DM-induced gene expression changes in the fetal umbilical cord. The raw gene expression profiles (ID: GSE51546) of umbilical cord tissue obtained from six normal mothers (non-diabetic) and six type 1 diabetic mothers were used to identify the differentially expressed genes. Genes that correspond to official gene symbols were selected for protein-protein interaction (PPI) and sub-network construction (combined score > 0.4). Functional annotation for Gene Ontology (GO) and pathway enrichment analysis were performed for genes involved in networking. A total of 110 differentially expressed genes were identified of which 38 were up-regulated while 72 were down-regulated. Only 37 genes were identified to significantly interact with each other. Hub genes including HSPA4, KCTD6, UBE2G1, FBXL19, and EHMT1 were up-regulated while KBTBD7, TRIM32, and NUP were down-regulated. T1DM had a major effect on the expression of genes involved in cellular death and differentiation, cell signaling and communication, protein modification and regulation of GTPase activity. Total 27 pathways were enriched and genes related to Wnt signaling, VEGF signaling, inflammation mediated by chemokine and cytokine signaling pathways, FGF signaling pathways and GnRH receptor pathways were found significantly affected by T1DM. Our results suggest that the T1DM environment seems to alter umbilical cord gene expression involved in the regulation of pathophysiology of the diabetic mother which in turn may lead to long-term consequences in various tissues in infants. This study provides insight into the molecular mechanism underlying the adverse pregnancy outcomes of maternal T1DM.

Use of automated fetal heart rate analysis to identify risk factors for umbilical cord acidosis at birth.

OBJECTIVE: To identify clinical parameters and intrapartum fetal heart rate parameters associated with a risk of umbilical cord acidosis at birth, using an automated analysis method based on empirical mode decomposition. METHODS: Our single-center study included 381 cases (arterial cord blood pH at birth pHa ≤7.15) and 1860 controls (pHa ≥7.25) extracted from a database comprising 8,383 full datasets for over-18 mothers after vaginal or caesarean non-twin, non-breech deliveries at term (>37 weeks of amenorrhea). The analysis of a 120-min period of the FHR recording (before maternal pushing or the decision to perform a caesarean section during labor) led to the extraction of morphological, frequency-related, and long- and short-term heart rate variability variables. After univariate analyses, sparse partial least square selection and logistic regression were applied. RESULTS: Several clinical factors were predictive of fetal acidosis in a multivariate analysis: nulliparity (odds ratio (OR) 95% confidence interval (CI)]: 1.769 [1.362-2.300]), a male fetus (1.408 [1.097-1.811]), and the term of the pregnancy (1.333 [1.189-1.497]). The risk of acidosis increased with the time interval between the end of the FHR recording and the delivery (OR [95%CI] for a 1-min increment: 1.022 [1.012-1.031]). The risk factors related to the FHR signal were mainly the difference between the mean baseline and the mean FHR (OR [95%CI]: 1.292 [1.174-1.424]), the baseline range (1.027 [1.014-1.040]), fetal bradycardia (1.038 [1.003-1.075]) and the late deceleration area (1.002 [1.000-1.005]). The area under the curve for the multivariate model was 0.79 [0.76; 0.81]. CONCLUSION: In addition to clinical predictors, the automated FHR analysis highlighted other significant predictors, such as the baseline range, the instability of the FHR signal and the late deceleration area. This study further extends the routine application of automated FHR analysis during labor and, ultimately, contributes to the development of predictive scores for fetal acidosis.

Discordance of umbilical coiling index between recipients and donors in twin-twin transfusion syndrome.

INTRODUCTION: To compare the intertwin umbilical cord coiling in twin-twin transfusion syndrome (TTTS) before fetoscopic laser treatment and to correlate these with Doppler findings in both twins. METHODS: We performed a prospective study using three-dimensional (3D) ultrasound with color Doppler imaging of the umbilical cord in TTTS. Coiling index was measured as a reciprocal value of one complete vascular coil. Ultrasound hypocoiling was thus defined as < 0.2 coils/cm and hypercoiling as > 0.6 coils/cm, respectively. Umbilical artery pulsatility index (PI) and peak systolic velocity, middle cerebral artery peak systolic velocity and ductus venosus PI of flow-velocity waveformes of both twins were measured. RESULTS: We included 65 women in the study. The average gestational age was 21.1 ±â€¯2.7 weeks. In 65 recipients and 56 donors coiling index could be quantified. The median (interquartile range) coiling index of recipient twins was significantly higher than of donors, 0.55 (0.41-0.68) vs. 0.26 (0.2-0.5); P < 0.0001. The proportions of abnormal intertwin coiling were significantly (P = 0.0015) different. Out of 65 recipient with coiling indices evaluation, 1 (1.5%) showed hypocoiled and 27 (41.5%) hypercoiled cords. In contrast, 27 donor twins (48.2%) showed hypocoiled and 5 (8.9%) hypercoiled umbilical cords. There were no significant correlations between the fetal Doppler values and coiling indices. DISCUSSION: Evaluation of umbilical cord coiling index using 3D color Doppler in both twins complicated by TTTS is feasible in both, donors and recipients. Coiling indices differ significantly between recipient and donor twins and do not correlate with Doppler findings.

Maternal Hematological Parameters and Placental and Umbilical Cord Histopathology in Intrauterine Growth Restriction.

OBJECTIVE: To investigate the placental and umbilical cord histopathology in intrauterine growth restriction (IUGR) and their relation to second-trimester maternal hematological parameters. MATERIALS AND METHODS: Patients were selected for the IUGR group based on estimated fetal weight below the 10th percentile. Patients were recruited into the control group randomly. Patients were followed up with ultrasound, and blood samples were taken between the 20th and 24th gestational weeks. After delivery and formalin fixation, weight and volume of the placenta were recorded and histologic samples were processed. RESULTS: Maternal platelet count strongly correlates with placental weight (r = 0.766). On the other hand, neonatal weight correlates with placental volume (r = 0.572) rather than with placental weight (r = 0.469). Umbilical arterial lumen cross-sectional area correlates with birth weight (r = 0.338). CONCLUSIONS: Maternal hematological parameters do not seem to affect neonatal outcome. Our main findings are the correlation of maternal platelet count with placental weight, the correlation of placental volume with birth weight being stronger than the correlation of placental weight with birth weight, and the correlation of umbilical artery lumen cross-sectional area with neonatal weight. Mild histopathologic alterations might occur in normal pregnancies; however, sufficient fetal nutrition can be maintained. This compensatory function of the placenta seems to be insufficient when two or more pathologies are present, which is characteristic for IUGR.

Excessive umbilical cord coiling confers risk of elevated nocturnal blood pressure and severe/early-onset preeclampsia.

BACKGROUND: The associations between umbilical cord coiling, feto-placental vascular resistance and maternal blood pressure (BP) are not well understood. METHOD: We retrospectively analyzed 502 pregnant women suspected of hypertensive disorders in the third trimester from a hospital-based cohort, who underwent ambulatory BP monitoring and umbilical artery Doppler velocimetry examinations within 14 days before delivery. By applying quantile regression, a significant quantile-dependent positive association between umbilical cord coiling index and umbilical artery pulsatility index (UAPIMOM; converted to multiples of median) was observed from above 0.75th quantiles for each parameter. RESULTS: Using the cutoffs both at the 0.75th quantile to define high umbilical cord coiling (≥0.28 coils/cm) and high UAPIMOM (≥1.30), respectively, a graded increase in BP level was observed from patients with both low, either high and both high categories. Multivariate linear and quantile regression revealed that the high umbilical cord coiling/high UAPIMOM interaction was significantly correlated with night-time mean DBP level. Moreover, umbilical cord hypercoiling (≥0.3 coils/cm) was significantly correlated with night-time DBP with an average increase of ∼5 mmHg from the 0.05th to 0.70th quantiles and independently predicted the occurrence of severe (odds ratio 2.32, 95% confidence interval: 1.22-4.41) and early-onset (odds ratio 2.43, 95% confidence interval: 1.18-4.97) preeclampsia after adjusting for covariates. Further mediation analysis showed that elevated high UAPIMOM (≥1.30) could explain 11.4% of the umbilical cord hypercoiling → high night-time DBP association. CONCLUSION: Therefore, this retrospective study identifies excessive umbilical cord coiling, and its interaction with increased feto-placental vascular resistance, as novel risk factors for nocturnal BP elevation and preeclampsia.

Effect of Milking Maneuver in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: To assess the short and medium-term effects of milking maneuver (MM) compared with early cord clamping for infants born before 37 weeks of pregnancy. MATERIAL AND METHODS: 138 infants between 24+0 and 36+6 weeks of gestation were allocated to MM or early cord clamping. Primary outcomes were the requirement of red blood cell transfusions or phototherapy. RESULTS: Initial hemoglobin was significantly higher in the MM group by 1.675 g/dL (p < 0.05) and initial hematocrit by 5.36% (p < 0.05), but no differences in the need of transfusion during the first 30 days after delivery were found (RR 0.8; 95% CI 0.22-2.85). Peak serum bilirubin was similar in both groups (11,097 ± 3.21 vs. 11,247 ± 3.56 mg/dL, p = 0.837). Phototherapy requirements were higher in the MM group (RR 1.62; 95% CI 1.1-2.38). No differences regarding the need of oral iron supplementation, platelet transfusion, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, periventricular leukomalacia, meconium aspiration syndrome, use of surfactant, days of oxygen supplementation, need of vasopressors, length of stay in the neonatal intensive care unit, or postpartum hemorrhage were found. CONCLUSION: MM does not reduce the need for red blood cell transfusions and increases phototherapy requirements in preterm infants.

Postnatal dilatation of umbilical cord vessels and its impact on wall integrity: Prerequisite for the artificial placenta.

INTRODUCTION: A lung assist device, which acts as an artificial placenta, can provide additional gas exchange for preterm and term newborns with respiratory failure. The concept of the lung assist device requires a large bore access via umbilical vessels to allow pumpless extracorporeal blood flow rates up to 30 mL/kg/min. After birth, constricted umbilical vessels need to be reopened for vascular access. The objective is to study the impact of umbilical vessel expansion on vessel integrity for achieving large bore access. METHODS: Umbilical cords from healthy term deliveries were cannulated and dilatated with percutaneous transluminal angioplasty catheters in 1 mm increments from 4 to 8 mm for umbilical artery and from 4 to 15 mm for umbilical vein, n = 6 per expansion diameter. Paraffin-embedded transverse sections of dilated and control samples were HE & Van Gieson stained. Effects of dilatation, shown by splitting, were measured. RESULTS: Umbilical vessel expansion led to concentric splitting, shown by areas devoid of extracellular matrix and nuclei in the tunica intima and media. No radial splitting was observed. Results suggest an expansion threshold of umbilical artery at 6 mm and umbilical vein at 7 mm, while maximal splitting was observed above this threshold (3.6 ± 0.8%, p = 0.043 for umbilical artery 7 mm and 6.3 ± 1.8%, p = 0.048 for umbilical vein 8 mm). Endothelial cell sloughing was present in all dilated samples but not in the control samples. CONCLUSION: The suggested thresholds for safe expansions are similar to in utero umbilical vessel diameters and demonstrate a proof of concept for attaining large bore access for the lung assist device.

Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs.

BACKGROUND: Physiologically based cord clamping (PBCC) has advantages over immediate cord clamping (ICC) during preterm delivery, but its efficacy in asphyxiated infants is not known. We investigated the physiology of PBCC following perinatal asphyxia in near-term lambs. METHODS: Near-term sheep fetuses (139±2 (SD) days' gestation) were instrumented to measure umbilical, carotid, pulmonary and femoral arterial flows and pressures. Systemic and cerebral oxygenation was recorded using pulse oximetry and near-infrared spectroscopy, respectively. Fetal asphyxia was induced until mean blood pressure reached ~20 mm Hg, where lambs underwent ICC and initiation of ventilation (n=7), or ventilation for 15 min prior to umbilical cord clamping (PBCC; n=8). Cardiovascular parameters were measured and white and grey matter microvascular integrity assessed using qRT-PCR and immunohistochemistry. RESULTS: PBCC restored oxygenation and cardiac output at the same rate and in a similar fashion to lambs resuscitated following ICC. However, ICC lambs had a rapid and marked overshoot in mean systemic arterial blood pressure from 1 to 10 min after ventilation onset, which was largely absent in PBCC lambs. ICC lambs had increased cerebrovascular injury, as indicated by reduced expression of blood-brain barrier proteins and increased cerebrovascular protein leakage in the subcortical white matter (by 86%) and grey matter (by 47%). CONCLUSION: PBCC restored cardiac output and oxygenation in an identical time frame as ICC, but greatly mitigated the postasphyxia rebound hypertension measured in ICC lambs. This likely protected the asphyxiated brain from cerebrovascular injury. PBCC may be a more suitable option for the resuscitation of the asphyxiated newborn compared with the current standard of ICC.