Influencia del pH de cordón umbilical en el resultado del cribado auditivo con otoemisiones en recién nacidos sanos / Influence of umbilical cord pH on the outcome of hearing screening with otoacoustic emissions in healthy newborns

Objetivo Es conocido el efecto de la hipoxia sobre el funcionamiento de las células ciliadas externas de la cóclea, que son las responsables de la respuesta a las otoemisiones utilizadas en el cribado auditivo neonatal. El objetivo de este estudio es conocer la influencia de variaciones leves o moderadas del pH de cordón umbilical al nacer en el resultado del cribado auditivo con otoemisiones en recién nacidos sanos sin factores de riesgo auditivo. Resultados La muestra está compuesta de 4.536 niños sanos. Los resultados no muestran diferencias significativas en el resultado del cribado auditivo entre el grupo de pH asfíctico (<7,20) y normal. Tampoco se detecta una cifra de pH inferior a 7,20 en la muestra que se relacione con alteración en el cribado. Desglosando en subgrupos con factores conocidos de variación en el resultado del cribado, como es el género o la lactancia, tampoco se detectan diferencias significativas de respuesta. El Apgar ≤ 7 sí se relaciona significativamente con un pH<7,20. Conclusiones En conclusión, las situaciones de asfixia leve-moderada asociadas al parto de recién nacidos sanos sin factores de riesgo auditivo no alteran el resultado del cribado con otoemisiones. (AU)

Objective The effect of hypoxia on the functioning of the outer hair cells of the cochlea, which are responsible for the response to otoemissions used in neonatal hearing screening, is well known. The aim of this study is to determine the influence of mild to moderate variations in umbilical cord pH at birth on the outcome of hearing screening with otoemissions in healthy newborns without hearing risk factors. Results The sample is composed of 4536 healthy infants. The results show no significant differences in the hearing screening outcome between the asphyctic (<7.20) and normal pH group. Nor is a figure below 7.20 detected in the sample that is related to an alteration in the screening. When broken down into subgroups with known factors of variation in the screening result, such as gender or lactation, no significant differences in response were detected. Apgar ≤ 7 is significantly related to pH<7.20. Conclusions In conclusion, mild-moderate asphyxia associated with delivery of healthy newborns, without auditory risk factors, does not alter the outcome of otoemission screening. (AU)

Effect of Extra-abdominal Vein Varix on the Stress Distribution in Umbilical Cord: A Simulation Study.

The umbilical cord is a critical structure linking the fetus to the placenta and is surrounded by the amniotic fluid. It is composed of a vein, two arteries coiled around the vein, and Wharton's jelly surrounding the blood vessels. In this study, the stress distribution of the arteries, vein, and Wharton's jelly of an umbilical cord with extra-abdominal umbilical vein varix is analyzed for varying amniotic pressure using finite element analysis. Four diameters are considered for the umbilical vein, 6.5 mm, 11 mm, 15.5 mm, and 20 mm, with 6.5 mm corresponding to the normal vein diameter. The amniotic pressure is varied from 15-105 mmHg in steps of 15 mmHg, to simulate contractions during labour. Stress distribution is obtained and the peak stresses are analyzed. According to the results, the peak stress in the Wharton's jelly and the umbilical vein increases nonlinearly with increasing amniotic pressure. The peak stress in umbilical arteries initially decreases till the amniotic pressure reaches 45 mmHg and thereafter increases. This might be due to asymmetric deformation of the Wharton's jelly at the pressure range below arterial pressure.Clinical Relevance- This study could be useful in understanding the fundamental mechanics of extra-abdominal umbilical vein varix and help in development of better treatment protocols.

Effect of different timings of umbilical cord clamping on the level of CD34+ cells in full-term neonates.

Despite the fact that delayed cord clamping (DCC) is recommended by many international organizations, early cord clamping is still widely practiced worldwide. The overarching goal of the DCC practice is to maximize neonatal benefits as achieving higher hemoglobin levels and decreasing the incidence of anemia as well as avoiding the adverse consequences. The current study was conducted to identify the effect of of DCC on the number of CD34+ stem cells in cord blood of full term neonates after two different timings (30 and 60 s after birth). One hundred and three full-term (FT) newborn babies (gestational age 37-40 weeks) delivered by elective cesarean section were randomly assigned into 2 groups: Group 1: babies were subjected to DCC 30 s after birth (50 newborns). Group 2: babies were subjected to DCC 60 s after birth (53 newborns). Neonates in group 2 had significantly higher levels of hemoglobin, hematocrit, total nucleated cells and CD34+ cells compared to those in group 1. The practice of DCC 60 s after birth achieved better CD34+ stem cells transfer in FT neonates than clamping the cord after 30 s.

Umbilical Cord Blood Use for Admission Blood Tests of VLBW Preterm Neonates: A Randomized Control Trial.

OBJECTIVE: Umbilical cord blood (UCB) for admission laboratories is an approach to decrease anemia risk in very low birth weight (VLBW) neonates. We hypothesized that UCB use results in higher hemoglobin concentration [HgB] around 24 hours of life. STUDY DESIGN: A randomized control trial among VLBW infants whose admission laboratories were drawn from UCB (n = 39) or the infant (n = 41) in three U.S. military NICUs (clinicaltrials.gov#NCT02103296). RESULTS: No demographic differences were observed between groups. UCB infants had higher [HgB] at 12 to 24 hours of life (15.5 vs. 14.0 g/dL, p = 0.02). The median time to first transfusion was 17 days longer in the experimental group (p = 0.04), and at discharge, their number of donor exposures was lower (1.1 vs. 1.8, p = 0.04). CONCLUSION: In the first 24 hours of life that is a period of higher risk for hemodynamic instability, UCB utilization for admission bloodwork in VLBW infants results in higher [HgB]. KEY POINTS: · Umbilical cord blood laboratory work in preterm infants is feasible.. · Cord blood use for admission laboratories results in increased hemoglobin in the first 24 hours of life.. · Cord blood use for admission laboratories delays time to first transfusion in preterm infants..

Tipos de partos y niveles de oxitocina, cortisol y hormonas tiroideas en plasma del cordón umbilical / Types of deliveries and levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma

Introducción: La placenta sintetiza y secreta varias hormonas que permiten la regulación del embarazo, el trabajo de parto y la adaptación metabólica materno-fetal. Su comportamiento asociado al tipo de parto puede dar información relevante sobre efectos epigenéticos. Objetivo: Describir el tipo de parto con los niveles de oxitocina, cortisol y hormonas tiroideas en plasma de cordón umbilical al nacer. Método: A 50 mujeres con embarazos principalmente normales se les cuantificaron los niveles neurohormonales en plasma de cordón umbilical, obtenido inmediatamente tras el periodo expulsivo. Los resultados se incorporaron a la base de datos clínicos de cada participante y se analizaron con Stata v.14.0. El protocolo fue aprobado por el comité de ética. Resultados: Hubo 33 partos vaginales (12 espontáneos, 13 acelerados y 8 inducidos) y 17 cesáreas (7 electivas y 10 de urgencia). Se observaron mayores niveles de cortisol en los partos vaginales acelerados; las cesáreas tuvieron menores niveles de cortisol y hormona estimulante de la tiroides. Las intervenciones clínicas, con altos o bajos niveles hormonales, están en directa relación con el tipo de parto. Conclusiones: El cortisol y la hormona estimulante de la tiroides medidos en plasma de cordón umbilical variaron según el tipo de parto. Esto es una primera cuantificación de hormonas en plasma de cordón umbilical y su posible regulación placentaria a propósito del tipo de parto.

Introduction: The placenta synthesizes and secretes several hormones allowing the regulation of pregnancy, labor and maternal-fetal metabolic adaptation. Their behavior associated with the type of delivery, may provide relevant information on epigenetic effects. Objective: To describe the type of delivery with the levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma at birth. Method: Neurohormonal levels from umbilical cord plasma obtained immediately post expulsion, were quantified in 50 women with mainly normal pregnancies. Results incorporated into the clinical database of each participant, statistically analyzed in Stata v.14.0. Protocol approved by ethics committee. Results: 33 were vaginal deliveries (12 spontaneous, 13 accelerated, 8 induced) and 17 cesarean sections (7 elective and 10 emergency). Higher cortisol levels were observed in accelerated vaginal deliveries, cesarean sections had lower cortisol and thyroid stimulating hormone levels. While clinical interventions, with high or low hormone levels, were related to the type of delivery. Conclusions: Cortisol and thyroid stimulating hormone measured in umbilical cord plasma varied according to the type of delivery. This is a first quantification of hormones in umbilical cord plasma and their possible placental regulation in relation to the type of delivery.

Umbilical Cord Collection and Drug Testing to Estimate Prenatal Substance Exposure in Utah.

OBJECTIVE: Our primary objective was to estimate statewide prenatal substance exposure based on umbilical cord sampling. Our secondary objectives were to compare prevalence of prenatal substance exposure across urban, rural, and frontier regions, and to compare contemporary findings to those previously reported. METHODS: We performed a cross-sectional prevalence study of prenatal substance exposure, as determined by umbilical cord positivity for 49 drugs and drug metabolites, through the use of qualitative liquid chromatography-tandem mass spectrometry. All labor and delivery units in Utah (N=45) were invited to participate. Based on a 2010 study using similar methodology, we calculated that a sample size of at least 1,600 cords would have 90% power to detect 33% higher rate of umbilical cords testing positive for any substance. Deidentified umbilical cords were collected from consecutive deliveries at participating hospitals. Prevalence of prenatal substance exposure was estimated statewide and by rurality using weighted analysis. RESULTS: From November 2020 to November 2021, 1,748 cords (urban n=988, rural n=384, frontier n=376) were collected from 37 hospitals, representing 92% of hospitals that conduct 91% of births in the state. More than 99% of cords (n=1,739) yielded results. Statewide, 9.9% (95% CI 8.1-11.7%) were positive for at least one substance, most commonly opioids (7.0%, 95% CI 5.5-8.5%), followed by cannabinoid (11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) (2.5%, 95% CI 1.6-3.4%), amphetamines (0.9%, 95% CI 0.4-1.5), benzodiazepines (0.5%, 95% CI 0.1-0.9%), alcohol (0.4%, 95% CI 0.1-0.7%), and cocaine (0.1%, 95% CI 0-0.3%). Cord positivity was similar by rurality (urban=10.3%, 95% CI 8.3-12.3%, rural=7.1%, 95% CI 3.5-10.7%, frontier=9.2%, 95% CI 6.2-12.2%, P=.31) and did not differ by substance type. Compared with a previous study, prenatal exposure to any substance (6.8 vs 9.9%, P=.01), opioids (4.7 vs 7.0% vs 4.7%, P=.03), amphetamines (0.1 vs 0.9%, P=.01) and THC-COOH (0.5 vs 2.5%, P<.001) increased. CONCLUSION: Prenatal substance exposure was detected in nearly 1 in 10 births statewide.

Optimization and application of a method to determine 24 perfluorinated compounds in umbilical cord serum by using liquid chromatography tandem mass spectrometry.

Perfluorinated compounds (PFCs) are a group of widely used synthetic chemicals. Owing to their unique chemical properties, PFCs can accumulate in the environment and living organisms. In vitro and in vivo studies have demonstrated the adverse effects of exposure to PFCs, resulting in increased concern. Therefore, a fast, reliable analytical method is crucial for human biomonitoring and health risk assessment. This study used two isotope internal standards to identify and quantify 24 PFCs in umbilical cord serum samples, based on classical liquid-liquid extraction (LLE) with liquid chromatography tandem mass spectrometry (LC-MS/MS). According to our review of the literature, this study is the first to determine the TFHSA, S4hPDS, S4hPOS, S4hPHS, SPHeS, SPNoS, and SPPeS by using this developed method. The average spiked recoveries of 24 PFCs were acceptable, ranging from approximately 64.0% to 124%; RSDs ranged from 0.74% to 11.2%; LOD and LOQ ranged from 0.013 to 0.248 µg/L and from 0.030 to 0.747 µg/L, respectively. This method was applied to measure the PFCs in umbilical cord serum samples; 24 PFCs were detected in the investigated samples, which are comparable to those reported in the literature. TFHSA, S4hPDS, S4hPOS, S4hPHS, SPHeS, SPNoS, and SPPeS were also detected in the samples, which should be investigated in further research. The sensitivity, accuracy, and precision of the developed method are sufficient for its application in large-scale biomonitoring studies.

Impact of interval between induction of spinal anesthesia to delivery on umbilical arterial cord ph of neonates delivered by elective cesarean section.

BACKGROUND: To evaluate the impact of interval between induction of spinal anesthesia to delivery of the fetus by elective cesarean section on umbilical arterial pH and neonatal outcome. PATIENTS AND METHODS: Two hundred and twenty pregnant women who were planned for elective cesarean section at term under spinal anesthesia were recruited. Minimum systolic, diastolic and mean arterial blood pressures (SBP, DBP, MAP) and largest pressure decrease (SBP, DBP, MPA) were also recorded. Induction of spinal anesthesia to delivery interval was measured. Following delivery, umbilical arterial cord analysis for pH and base deficit were done. Apgar scores at 1 min and at 5 min, neonatal intensive care unit (NICU) admission, need for mechanical ventilation and incidence of hypoxemic-ischemic encephalopathy were recorded. RESULTS: Induction of spinal anesthesia to delivery interval was 25.7 ± 5.6 min. Lowest SBP and MAP reached during cesarean delivery were 88.9 ± 7.3 mmHg and 60.4 ± 5.6 mmHg, respectively. MAP < 65 mmHg was reached in 136 (62%) patients with a decrease of MAP of > 20% in 149 (68%) patients. Duration of the longest hypotension episode was 3.3 ± 2.2 min. All patients required ephedrine administration for hypotensive episodes with an average dosage of 11.4 ± 3.2 mg. Umbilical pH of 7.3 ± 0.1 and base deficit of 8.3 ± 4.4 mmol/l were recorded. Apgar scores at 5 min were 8.5 ± 1.2. Eight (3.6%) neonates were admitted in the NICU. One neonate needed mechanical ventilation. There were no cases of hypoxemic-ischemic encephalopathy. There were inverse correlations between induction of spinal anesthesia to delivery interval, body mass index (BMI) and duration of longest hypotension episode in relation to umbilical pH (r = -0.817, -0.395 and -0.268, respectively). Cut off value for induction of spinal anesthesia to delivery interval greater than 27 min predicted an umbilical pH of < 7.2. Cut off value for the duration of the longest hypotension episode greater than 5 min predicted an umbilical pH of < 7.2. Cut off value for BMI greater than 35 kg/m2 predicted an umbilical pH of < 7.2. CONCLUSION: Prolonged interval between induction of spinal anesthesia to delivery could be associated with neonatal acidosis. This could be aggravated by maternal obesity and prolonged duration of hypotension episodes during cesarean delivery.

Impact of a delayed cord clamping protocol on maternal and neonatal outcomes in patients undergoing term cesarean section.

OBJECTIVE: Given concerns amongst physicians and other maternity providers for increased maternal blood loss with delayed cord clamping, our objective was to determine the impact of routine delayed clamping with term cesarean section on maternal blood loss metrics. STUDY DESIGN: A retrospective cohort study evaluated the impact of delayed cord clamping in term cesareans at our tertiary care center following protocol implementation. The pre-protocol group (PRE) ranged 1 October 2015 to 31 March 2016. The post-protocol (POST) group ranged 1 October 2017 to 31 March 2018. The primary outcome was maternal estimated blood loss (EBL) during cesarean section. Secondary outcomes included maternal transfusion, hemorrhage (EBL > 1,000 mL), and changes in hemoglobin (Hgb) and hematocrit (HCT). Neonatal outcomes were APGAR scores at 1 and 5 min. RESULTS: 733 subjects were included, (PRE = 416, POST = 317). Overall 44.7% reported prior cesarean section. Preop differences included only platelets k/µL (222 vs. 211, p = .015), Hgb g/dL (11.7 vs. 11.9, p = .002) and HCT% (36.2 vs. 35.2, p = .027), with Hgb and HCT differences in opposite clinical directions. EBL actually decreased after the delayed cord clamping protocol (p = .04). The median [interquartile range] was the same (700 [600-800]), but the PRE group had higher proportions of EBL 800-1,000 (16% vs. 11%) and EBL > 1,000 (4.3% vs 3.7%) comprising this statistical difference. There was no difference in maternal transfusion (2.2%), hemorrhage (11.1%), or change in Hgb (Δ = -1.6 g/dL) or HCT (Δ = -4.6%), (all p > .05). APGAR scores were slightly lower in the POST group at 1 min (8 [8-9] vs. 9 [8-9], p = .035) but similar by 5 min (9 [9-9], p = .38). CONCLUSION: Concerns for increased maternal blood loss during cesarean delivery after implementing a routine delayed cord clamping protocol were not supported. While EBL was lower with delayed cord clamping, all differences between groups appear to lack clinical significance. This offers reassuring evidence there is no negative impact on maternal hematologic characteristics including blood loss from the delayed cord clamping protocol.

Umbilical Cord Management in Late Preterm and Term Infants: A Randomized Controlled Trial.

OBJECTIVE: The study aimed to compare the effects of three different methods of umbilical cord management on hematological parameters in term and late-preterm infants. STUDY DESIGN: A randomized controlled trial comparing intact-umbilical cord milking (I-UCM) with cut-umbilical cord milking (C-UCM) and immediate cord clamping (ICC) in neonates born >35 weeks' gestation. RESULTS: A total of 587 infants were evaluated. Of these, 197 were assigned to I-UCM, 190 to C-UCM, and 200 to ICC. Mean hemoglobin and hematocrit levels at 48 hours of age were higher in I-UCM group compared with the ICC group (p = 0.002 and p = 0.010, respectively). CONCLUSION: These findings suggest that I-UCM is more beneficial choice. Further trials are needed to assess the various long- and short-term effects of different cord milking methods. KEY POINTS: · This is the first study comparing these three methods (I-UCM, C-UCM, and ICC) concurrently.. · I-UCM is more beneficial choice.. · Although the terms I-UCM and C-UCM are often used interchangeably, these are different procedures..

Umbilical cord milking versus delayed cord clamping in term and late-preterm infants: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to compare the efficacy and safety of umbilical cord milking (UCM) versus delayed cord clamping (DCC) in term and late-preterm infants. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Clinical trial registries, and Gray literature were searched for randomized controlled trials (RCTs) comparing UCM with DCC in term and late-preterm infants for both short-term and long-term outcomes. Intact and cut UCM were compared separately with DCC using subgroup analysis. We used fixed effect model to pool the data. Random effects model was used when there was significant heterogeneity. RESULTS: Nine studies (1632 infants) were included in the systematic review. Milking was performed on intact cord (i-UCM) in five studies (n = 829) and on cut cord (c-UCM) in four studies (n = 803). Cord milking significantly improved hemoglobin level at 48-72 h of life when compared to DCC (six studies, n = 924, mean difference 0.36 g/dL; 95% CI: 0.19-0.53). In addition, hemoglobin level at six to eight weeks of age was also significantly higher in the studies comparing i-UCM with DCC (two studies, n = 550: mean difference 0.16 g/dL; 95% CI: 0.06-0.27). There was no difference between the UCM group and DCC group for any other outcome. Only one study provided information on growth and hematological parameters at one year of age. Neurodevelopmental outcomes were not reported. None of the studies included non-vigorous infants. The grade of evidence was low to very low for all the outcomes studied. CONCLUSION: UCM is comparable to DCC in improving short-term hematological outcomes in term and late-preterm vigorous infants. Trials assessing the effect of UCM on important clinical and long-term outcomes among non-vigorous mature preterm infants are urgently required.

Maternal exposure to fine particulate matter over the first trimester and umbilical cord insertion abnormalities.

BACKGROUND: Our hypothesis was that exposure to fine particulate matter (PM2.5) is related to abnormal cord insertion, which is categorized as a form of placental implantation abnormality. We investigated the association between exposure to total PM2.5 and its chemical components over the first trimester and abnormal cord insertion, which contributes to the occurrence of adverse birth outcomes. METHODS: From the Japan Perinatal Registry Network database, we used data on 83 708 women who delivered singleton births at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). We collected PM2.5 on a filter and measured daily concentrations of carbon and ion components. Then, we calculated the average concentrations over the first trimester (0-13 weeks of gestation) for each woman. A multilevel logistic-regression model with the hospital as a random effect was used to estimate the odds ratios (ORs) of abnormal cord insertion. RESULTS: Among the 83 708 women (mean age at delivery = 33.7 years), the frequency of abnormal cord insertion was 4.5%, the median concentration [interquartile range (IQR)] of total PM2.5 was 16.1 (3.61) µg/m3 and the OR per IQR for total PM2.5 was 1.14 (95% confidence interval = 1.06-1.23). In the total PM2.5-adjusted models, total carbon, organic carbon, nitrate, ammonium and chloride were positively associated with abnormal insertion. Organic carbon was consistently, and nitrate tended to be, associated with specific types of abnormal insertion (marginal or velamentous cord insertion). CONCLUSIONS: Exposure to total PM2.5 and some of its components over the first trimester increased the likelihood of abnormal cord insertion.

Predicting Maternal-Fetal Disposition of Fentanyl Following Intravenous and Epidural Administration Using Physiologically Based Pharmacokinetic Modeling.

Fentanyl is an opioid analgesic used to treat obstetrical pain in parturient women through epidural or intravenous route, and unfortunately can also be abused by pregnant women. Fentanyl is known to cross the placental barrier, but how the route of administration and time after dosing affects maternal-fetal disposition kinetics at different stages of pregnancy is not well characterized. To address this knowledge gap, we developed a maternal-fetal physiologically based pharmacokinetic (mf-PBPK) model for fentanyl to evaluate the feasibility to predict the maternal and fetal plasma concentration-time profiles of fentanyl after various dosing regimens. As fentanyl is typically given via the epidural route to control labor pain, an epidural dosing site was developed using alfentanil as a reference drug and extrapolated to fentanyl. Fetal hepatic clearance of fentanyl was predicted from CYP3A7-mediated norfentanyl formation in fetal liver microsomes (intrinsic clearance = 0.20 ± 0.05 µl/min/mg protein). The developed mf-PBPK model successfully captured fentanyl maternal and umbilical cord concentrations after epidural dosing and was used to simulate the concentrations after intravenous dosing (in a drug abuse situation). The distribution kinetics of fentanyl were found to have a considerable impact on the time course of maternal:umbilical cord concentration ratio and on interpretation of observed data. The data show that mf-PBPK modeling can be used successfully to predict maternal disposition, transplacental distribution, and fetal exposure to fentanyl. SIGNIFICANCE STATEMENT: This study establishes the modeling framework for predicting the time course of maternal and fetal exposures of fentanyl opioids from mf-PBPK modeling. The model was validated based on fentanyl exposure data collected during labor and delivery after intravenous or epidural dosing. The results show that mf-PBPK modeling is a useful predictive tool for assessing fetal exposures to fentanyl opioid therapeutic regimens and potentially can be extended to other drugs of abuse.

Clinically relevant umbilical cord inflammation identified based on CD15-associated vasculitis patterning.

INTRODUCTION: Acute funisitis, a granulocyte-related inflammation of the umbilical cord, is associated with chorioamnionitis and perinatal adverse events. However, there is no efficient procedure for detecting clinically relevant umbilical cord inflammation. The objective of this study was to identify such inflammation, based on immunohistochemical assessment of umbilical cord vasculitis patterns. METHODS: Accordingly, 261 cases were retrieved from a single medical institute. Using the well-established granulocyte marker CD15, we developed a five-tier umbilical cord inflammation-scoring system. Additionally, previous morphological assessments from pathological reports were compared to the immunohistochemical findings. RESULTS: Analysis of results based on our new scoring system revealed that severe umbilical phlebitis (score 3) was significantly associated with maternal inflammatory response and that severe umbilical arteriophlebitis (score 4) was correlated with low umbilical arterial blood pH, a feature linked to fetal mortality and morbidity. These results corresponded with and were validated by the morphology-based assessments. Additionally, immunohistochemical analysis revealed the clinical and pathological relevance of vitelline vasculitis, a recently proposed condition. We found that analyzing three umbilical cord sections enabled superior detection of severe umbilical vasculitis than analyzing two sections. However, whether these sections were sampled from multiple distant sites or a single localized site did not significantly affect the detection of clinically relevant inflammation. DISCUSSION: CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation. CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation.

Assessment of biological matrices for the detection of in utero cannabis exposure.

Cannabis consumption has been increasing worldwide among pregnant women. Due to the negative effects of prenatal cannabis exposure, it is necessary to develop an objective, sensitive, and specific method to determine cannabinoids use during pregnancy. In this study, we compared four different biological samples, maternal hair, meconium, umbilical cord, and placenta, for the detection of in utero cannabis exposure. The biological samples were collected from 627 mother-newborn dyads. All hair and meconium samples were analyzed, and umbilical cord and placenta if hair and/or meconium were positive for cannabinoids. Meconium and hair showed to complement each other, with an agreement between hair and meconium results of 96.7% but only 34.3% if just positive results were considered. Umbilical cord and placenta results showed a better agreement with meconium (91.3% and 92.6%, respectively) than with hair (39.1% and 34.6%, respectively). The predominant metabolites in meconium were 11-nor-carboxy-THC (THCCOOH) and 8,11-dihydroxy-THC (diOHTHC), and in umbilical cord and placenta was THCCOOH-glucuronide. Cannabidiol (CBD) and cannabinol (CBN) were detected in meconium but not in any umbilical cord or placenta. For the first time, prenatal marijuana exposure was analyzed and compared in paired hair, meconium, umbilical cord, and placental samples. Hair and meconium positivity rate was similar, but a more sensitive and specific analytical method for the hair may resolve discrepancies between the matrices. Umbilical cord and placenta may be considered suitable alternative matrices to meconium through the determination of THCCOOH-glucuronide as a biomarker of cannabis exposure.

Effects of passage through the digestive tract on incretin secretion: Before and after birth.

AIMS/INTRODUCTION: It was reported that fetuses secrete endogenous incretin; however, the stimulants of fetal incretin secretion are not fully understood. To investigate the association between the passage of amniotic fluid through the intestinal tract and fetal secretion of incretin, we analyzed umbilical cord incretin levels of infants with duodenum atresia. MATERIALS AND METHODS: Infants born from July 2017 to July 2019 (infants with duodenum atresia and normal term or preterm infants) were enrolled. We measured and compared the concentrations of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP) in the umbilical vein and preprandial blood samples after birth. RESULTS: A total of 98 infants (47 term, 46 preterm and 5 with duodenum atresia) were included. In patients with duodenum atresia, umbilical vein GLP-1 and GIP levels were the same as those in normal infants. In postnatal samples, there were positive correlations between the amount of enteral feeding and preprandial serum concentrations of GLP-1 (r = 0.47) or GIP (r = 0.49). CONCLUSIONS: Our results show that enteral feeding is important for secretion of GLP-1 and GIP in postnatal infants, whereas the passage of amniotic fluid is not important for fetal secretion of GLP-1 and GIP. The effect of ingested material passing through the digestive tract on incretin secretion might change before and after birth. Other factors might stimulate secretion of GLP-1 and GIP during the fetal period.

Drug testing in biological samples vs. maternal surveys for the detection of substance use during whole pregnancy.

BACKGROUND: Early diagnosis of nicotine, ethanol and drug use during pregnancy is critical in order to provide adequate care. Current screening procedures show limitations in terms of reliability and short windows of detection. OBJECTIVES: To investigate the prevalence and identify biomarkers of substance use and changes in substance use during pregnancy. To compare drug testing results in different types of biological samples (maternal hair, meconium, placenta, umbilical-cord) with self-reported data. PARTICIPANTS AND SETTING: Prospective cohort study using data from pregnant women and their newborns. METHODS: Biological matrices were collected at birth and analyzed by liquid chromatography tandem mass spectrometry. A paper survey was provided to determine substance use habits. RESULTS: 867 mother-newborn pairs were included. According to the analysis of biological samples, 29.1% cases were positive for one or more substances (13.6% nicotine, 8.4% ethanol, 8.3% cocaine, 6.4% cannabis, 5.7% opioids). The profile of the substance-using mother was a single woman, <28 years-old, with no higher education and unemployed. Segmental maternal hair analysis showed a decrease in tobacco, cannabis and cocaine use throughout pregnancy (p < 0.001). The level of concordance between results from interviews and from biological analyses was weak for opioids, cocaine, and cannabis (kappa coefficient < 0.40). Maternal hair detected the highest number of cases, followed by meconium and by placenta and/or umbilical-cord. CONCLUSIONS: Maternal survey was not a reliable screening technique. Analysis of maternal hair detected the highest number of cases with the broadest detection window (whole pregnancy).

Umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (ßCTX) levels in term pregnancies with vitamin D deficiency.

AIMS: The aim of the present study was to evaluate umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (ßCTX) levels in term pregnancies with vitamin D deficiency. MATERIALS AND METHODS: Ninety-two pregnant women between 19 and 35-years-old who delivered at term gestational age were included in the study and divided into deficient (n = 32), insufficient (n = 30), and normal (control) vitamin D levels (n = 30). RESULTS: Maternal demographic characteristics and biochemical parameters were similar among groups. The mean umbilical cord P1NP level was 221.4 (211.7-231.0, 95%CI) pg/mL in the vitamin D deficiency group, 282.5 (271.2-293.8, 95%CI) pg/mL in the vitamin D insufficiency group, and 280.9 (270.9-290.8, 95%CI) pg/mL in the control group and significantly lower in vitamin D deficiency group than others (p < .001). Umbilical cord P1NP level was similar in the vitamin D insufficiency group and control group (p = .971). The mean umbilical cord ßCTX level was 5530, 9 (5511.5-5550.3, 95%CI) pg/mL in the vitamin D deficiency group, 5516.3 (5498.4-5534.2, 95%CI) pg/mL in the vitamin D insufficiency group, and 5510 (5491.4-5528.5, 95%CI) pg/mL in the control group, which was statistically similar among the groups (p = .251). CONCLUSION: Our results indicated that vitamin D deficiency during pregnancy affects fetal bone osteoblast activity.

Rare earth elements in umbilical cord and risk for orofacial clefts.

Questions remain about the effects of rare earth elements (REEs) on reproductive health, and no study has explored in utero exposure to REEs and risk of orofacial clefts (OFCs). We recruited subjects from a case-control study conducted in Shanxi Province, China. Concentrations of fifteen REEs were quantified in umbilical cord samples by means of Inductively Coupled Plasma Mass Spectrometry measurements. We employed logistic regression and weighted quantile sum (WQS) regression models to estimate the association between REEs exposures and OFCs. Of 226 subjects included in our study, 34 were cleft lip only, 44 were cleft lip with cleft palate and 6 were cleft palate only. In the logistic regression model, concentrations above the median of all subjects were associated with an increased OFCs risk of 2.35-fold (95% CI: 1.22, 4.53) for Lanthanum and 2.12-fold for Neodymium (95% CI: 1.10, 4.10) adjusting for maternal age, BMI, gestational weeks, sex of infants and passive smoking. In WQS model, a quartile increase in the index resulting in an increase of 3.10 (95% CI: 1.38, 6.96) in the odds of OFC. Lanthanum and Neodymium were suggested to be important factors. The results were largely consistent for OFC subtypes. In conclusion, in utero exposure to mixtures of REEs increased the risk of OFCs. Lanthanum and Neodymium were likely to be important factors in the development of OFCs.

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs (miRNAs) have been highlighted in human cancers. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-451a on hepatocellular carcinoma (HCC) remains further investigation. Our study aims to explore the impact of exosomal miR-451a on the progression of HCC. Expression of miR-451a and a disintegrin and metalloprotease 10 (ADAM10) in HCC tissues and adjacent normal tissues were determined. The exosomes were extracted from hucMSCs and co-cultured with Hep3B and SMMC-7721 cell lines. After the treatment of relative exosomes or exosome inhibitor GW4869 in Hep3B and SMMC-7721 cells, the paclitaxel resistance and malignant phenotypes of HCC cells were measured. Moreover, the effect of hucMSCs-derived exosomes on the expression of miR-451a and ADAM10 in HCC cells was assessed. The targeting relationship between miR-451a and ADAM10 was verified to detect the impact of ADAM10-wild type and ADAM10-mutant type (MUT) on HCC cell processes. Low expression of miR-451a and high expression of ADAM10 indicated a poor prognosis of HCC patients. MiR-451a was up-regulated while ADAM10 was down-regulated in HCC cells after co-culture with HucMSC-derived exosomes. The exosomes elevated miR-451a and inhibited ADAM10 to suppress the paclitaxel resistance, cell cycle transition, proliferation, migration and invasion, and promote apoptosis of HCC cells. ADAM10 was verified to be a target gene of miR-451a. ADAM10-MUT promoted HCC process independent of miR-451a mimic. HucMSC-derived exosomal miR-451a could restrict the epithelial-mesenchymal transition of HCC cells by targeting ADAM10, which might provide new targets for HCC treatment.