Management of cord and placental blood and its effect upon the newborn

A comparative study was made of erythrocyte counts and weights of the newborn at term. Three groups were used: Cases in which the cord was clamped at once, those in which the cord was allowed to pulsate five minutes, and those in which the cord and placental blood was stripped into the baby. Standards and procedure were set up so that there would be a minimum of error. Evidence was elicited showing that babies in the "pulsating" and the "stripped" groups received a significant amount of blood which was beneficial. The amount varied, but when the stripping method was used, the term baby received about 100 cc. of blood.Babies receiving this blood had higher erythrocyte counts, higher hemoglobin values, higher initial weights, less weight loss, and less rapid loss of weight. It is believed the additional blood supplied is of benefit especially to prematures and to those infants who are in any degree of shock following long labors, difficult deliveries, abruptio placenta, placenta previa, or compression of the cord. The added blood benefits the baby by combating the initial shock, by aiding in filling the capillary bed of the expanding lungs, by increasing iron reserve, by lessening demand upon blood-forming organs (especially in prematures), by protecting the breakdown of body proteins and by aiding the transition from one source of oxygen to another. Five minutes, as a rule, is not long enough to wait for pulsation if the baby is to receive its quota of available blood. Stripping of cord and placental blood into the infant is not a harmful procedure when done gently and is particularly useful in cases where the condition of the mother or child is such that it is inadvisable to wait for the uterus to force the blood physiologically into the child. The additional blood does not cause icterus. The pulsating of the umbilical cord plays only a minor role in the process by which the baby receives blood after the second stage of labor. The pressure of the uterine contractions upon a blood-filled placenta, forcing blood through the umbilical vein into the child, plays the major role. Pitocin and/or ergot preparations would aid in this process. Anemic mothers have a tendency toward having anemic babies. Venous pressure experiments using a phlebaumanometer showed pressures before and after stripping, the force of uterine contractions on the umbilical vein pressure and the variation in pressure with crying and at rest. The giving of 100 cc. of blood by stripping affects the venous pressure of the child very little, if done slowly. If the stripping is done rapidly, there is a transient rise with a return to normal within a few minutes.A survey of 1,900 diplomates of the American Board of Obstetrics and Gynecology showed that there is wide variation in the management of cord and placental blood. Of 455 specialists who stripped the cord, five thought there was some increase in icterus, and one reported cardiovascular distress.     

Molecular evidence suggesting the persistence of residual SARS‐CoV‐2 and immune responses in the placentas of pregnant patients recovered from COVID‐19

ObjectivesRecent studies have shown the presence of SARS‐CoV‐2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high‐risk group for COVID‐19. Based on these findings, we assessed SARS‐CoV‐2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID‐19 and cytokine fluctuations in maternal and foetal tissues.Materials and MethodsRemnant SARS‐CoV‐2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS‐CoV‐2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay.ResultsResidual SARS‐CoV‐2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly.ConclusionsOur study showed that SARS‐CoV‐2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.     

Heterogeneous histochemical reaction pattern of the lectin Bandeiraea (Griffonia) simplicifolia with blood vessels of human full-term placenta

Bandeiraea simplicifolia lectin (BS-I) stains vascular endothelium in various species. In humans, less than 10% of the specimens studied exhibit a reaction with BS-I. In the present histochemical study, the reactivity of BS-I with placental blood vessels and its correlation with the blood group from mother and newborn child was investigated. Acetone-fixed cryosections of representative tissue segments of human full-term placenta and umbilical cord were stained with BS-I. The staining pattern of tissues from patients with different blood groups was identical, although the reaction of BS-I in the placenta was heterogeneous. BS-I did not react with the umbilical cord. Vascular smooth muscle cells at the insertion site of the umbilical cord into the chorionic plate, and endothelium deeper in the chorionic plate, became progressively stained. The endothelial cells and tunica muscularis of smaller arteries and veins in stem villi lost their reactivity in parallel with decreasing vessel size. Arterioles and venules reacted heterogeneously. Capillaries, trophoblastic basement membranes, especially epithelial plates, and sometimes the syncytiotrophoblast were labelled in several terminal villi. The data indicate that 1) the placenta binds BS-I to fetal endothelium independent of the blood group, 2) cell-surface antigens on placental endothelial cells are expressed heterogeneously and 3) cell-surface glycans are constituted in an organ-specific manner on human endothelial cells.     

Hemodynamic analysis of Hyrtl anastomosis in human placenta

The Hyrtl anastomosis is a common connection between the umbilical arteries near the cord insertion in most human placentas. It has been speculated that it equalizes the blood pressure between the territories supplied by the umbilical arteries. However, its functional role in the regulation and distribution of fetal blood flow to the placenta has not yet been explored. A computational model has been developed for quantitative analysis of hemodynamic characteristic of the Hyrtl anastomosis in cases of discordant blood flow in the umbilical arteries. Simulations were performed for cases of either increased placental resistance at the downstream end or reduced arterial blood flow due to some pathologies upstream of one of the arteries. The results indicate that when placental territories of one artery impose increased resistance to fetal blood flow, the Hyrtl anastomosis redistributes the blood flow into the second artery to reduce the large pressure gradients that are developed in the affected artery. When one of the arteries conducts a smaller blood flow into the placenta and a relatively smaller pressure gradient is developed, the Hyrtl anastomosis rebuilds the pressure gradients in the affected artery and redistributes blood flow from the unaffected artery to the affected one to improve placental perfusion. In conclusion, the Hyrtl anastomosis plays the role of either a safety valve or a pressure stabilizer between the umbilical arteries at the placental insertion.     

Individual anatomical variability of arteries of the fetal surface of human placenta

Two hundred and ten placentas of 36-40-week-old pregnancies, terminating in birth of a functionally full-bodied child have been investigated. The placental arteries form is compared with the form of the placenta, with the place of the umbilical cord fixation, with the placental areas, with the number of the umbilical arteries, etc. A close connection is stated between the form of the placenta and its arterial bed. Round, oval, triangle placentas at a certain position of the umbilical cord root are characterized with loose forms of the arteries, while at a lateral, marginal and membranous types of the umbilical cord fixation magistral forms predominate. Curved, crescent, S-form, wavy loop-like forms of the main arterial magistral on the foetal surface of the placenta are also considered as magistral ones. The loose forms are noted in placentas with additional lobuli and in multilobular placentas. There is a definite dependence between forms of the arteries, area of the placenta and amount of cotyledons. At one marginal form one arterial magistral has been found, it successively branches along the whole placenta, at another magistral form the umbilical arteries divide into 12 sectorial branches.     

Prostacyclin producing activity of human umbilical, placental and uterine vessels

Prostacyclin-like material producing activity of umbilical, placental and uterine vessels was studied.Umbilical arteries and veins were separated at sites 10–15 cm and 1–2 cm from insertion of the umbilical cord to the placenta. Placental arteries and veins were prepared from the first, second and third branches on the chorionic plate. Uterine vessels were obtained at abdominal hysterectomy.After incubation of each specimen in Tris buffer 1 ml (pH8.5, 0.5M) for 30 min at room temperature, the inhibitory effect of the medium on ADP induced platelet aggregation was measured and the prostacyclin-like material was quantified. These procedures were repeated consecutively four times in total for each specimen. Prostacyclin-like material production rate and its total production were calculated.In total prostacyclin-like material production, umbilical arteries and veins were much higher than placental arteries and veins respectively (p<0.001), but there was no significant difference between placental and uterine vessels.These results showed that prostacyclin-like material producing activity of blood vessels declined remarkably at the transitive region from umbilical to placental vessels. It seems that this distribution of vascular prostacyclin-like material producibility in the fetoplacental vascular system correlates with that of vascular reactivity to prostacyclin.     

The effects of prostacyclin and thromboxane analogue (U46619) on the fetal circulation and umbilical flow velocity waveforms

In placental insufficiency and pre-eclampsia the relative production rates of prostacyclin and thromboxane by the placenta and umbilical vessels are altered and the Doppler umbilical flow velocity waveform shows a high resistance pattern. To investigate the control of umbilical placental blood flow by those eicosanoids either prostacyclin (10 micrograms/min), or the thromboxane analogue U46619 (10 ng/min) was infused into the distal aorta of 12 chronically catheterized fetal lambs at day 125. Thromboxane produced a rise in mean arterial pressure and a rise in the systolic diastolic ratio of the umbilical artery flow waveform (2.6 to 3.1; P less than 0.05). Umbilical blood flow did not change and there was no evidence of altered flow to other organs. Prostacyclin caused a fall in fetal mean arterial pressure and a decrease in the umbilical artery systolic diastolic ratio (2.9 to 2.4; P less than 0.05). Prostacyclin produced a three-fold increase in lung perfusion (and the onset of fetal breathing movements) and this was associated with a 90% reduction in muscle blood flow (hindlimb muscle flow reduced from 12.5 to 1.1 ml.min-1 100g-1; P less than 0.01). We conclude that the local release of thromboxane in the fetal placental vascular bed could account for the rise in systolic diastolic ratio seen in umbilical placental insufficiency.     

Ventilation Onset Prior to Umbilical Cord Clamping (Physiological-Based Cord Clamping) Improves Systemic and Cerebral Oxygenation in Preterm Lambs

BackgroundAs measurement of arterial oxygen saturation (SpO₂) is common in the delivery room, target SpO₂ ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.AimWe investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.MethodsSystemic and cerebral blood-flows, pressures and peripheral SpO₂ and regional cerebral tissue oxygenation (SctO₂) were measured continuously in apnoeic preterm lambs (126±1 day gestation). Positive pressure ventilation was initiated either 1) prior to umbilical cord clamping, or 2) after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.ResultsClamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO₂ and SctO₂, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5–6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.ConclusionThe establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO₂ nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.     

Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome

Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48–0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15–14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31–36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy outcomes.     

Innate Immune Function in Placenta and Cord Blood of Hepatitis C – Seropositive Mother-Infant Dyads

Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV) infection. In contrast to the adult population who develop persistent viremia in ∼80% of cases following exposure, the rate of mother-to-child transmission (2–6%) is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood) and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and γδ-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.     

17 beta-Hydroxysteroid oxidoreductase activity in human maternal and umbilical cord sera

The specific activity of 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR) in human umbilical cord arterial serum has been reported to be similar to that of maternal serum and 5- to 15-times higher than that of cord venous serum. Based on these findings, it was proposed that 17 beta-HSOR in cord arterial serum arises from fetal tissue sources other than placenta. In the course of studies of the role of 17 beta-HSOR in the modulation of bioactive estrogen levels in the human fetus, we determined that: (i) the specific activity of 17 beta-HSOR in maternal serum is 2.1- to 55-times higher than that in either umbilical cord venous serum or cord arterial serum; (ii) the specific activity of 17 beta-HSOR in umbilical cord venous and cord arterial sera are similar; (iii) anti-human placental cytosolic 17 beta-HSOR antibody inactivates the 17 beta-HSOR in maternal, umbilical cord arterial, and cord venous sera but not in maternal or fetal erythrocytes; (iv) the specific activity of 17 beta-HSOR in maternal serum (expressed per mg protein) is higher than that in umbilical cord serum and maternal and fetal erythrocytes, and is approximately 700-times lower than that of the placental microsomal enzyme; (v) the preferred cofactor for maternal serum 17 beta-HSOR is NADP+; (vi) 17 beta-HSOR is associated with the high speed supernatant fraction of maternal serum rather than with the particulate fraction; and, (vii) the patterns of binding of [3H]estradiol-17 beta to proteins in maternal and umbilical cord arterial sera and those of 17 beta-HSOR activity, determined in corresponding fractions obtained after sucrose density gradient centrifugation, are approximately coincidental at S20, omega 4.6-5. The findings of higher 17 beta-HSOR levels in maternal serum compared with umbilical cord arterial serum and the inactivation of the cord arterial serum enzyme by an antibody that recognizes human placental cytosolic 17 beta-HSOR is suggestive that 17 beta-HSOR in cord arterial serum is of placental origin.     

Stem cells from umbilical cord and placenta for musculoskeletal tissue engineering

Mesenchymal stem cells isolated from amnion/amniotic fluid, umbilical cord blood, placental tissue, umbilical cord vein and the Wharton's Jelly are promising candidates for musculoskeletal tissue engineering of bone and cartilage tissues. The extracorporeal nature of this source avoids the ethical concerns that plague the isolation of embryonic stem cells. Moreover, the harvesting does not require the invasive and discomfort extraction procedures as well as patient risks that attend adult stem cell isolation. Current preclinical studies support the application of these cell-based therapies for the regeneration of musculoskeletal tissues. We performed a review of the literature to focus on actual knowledge and the future perspectives of the stem cells deriving from umbilical cord and placenta for musculoskeletal tissue engineering.     

Immunohistochemistry of carbonic anhydrase in human placenta and fetal membranes

The localization of human carbonic anhydrase (CA) isoenzymes HCA I, HCA II, and rat CA II have been studied in human umbilical cord, chorion laeve including amnion and placenta from first and second trimester and also from term pregnancies. Detection techniques of immunofluorescence and immunoperoxidase were used in cryostat and paraffin sections. Both isoenzymes were found in the villous syncytiotrophoblast throughout pregnancy. HCA I staining patterns in the villous endothelium were highly variable whereas increasing immunoreactivity levels of endothelial HCA II were detected as pregnancy advances. The extravillous cytotrophoblast showed generally weaker levels of immunoreactivity. In amnionic epithelium of membranes, chorionic plate and umbilical cord, higher activities for HCA I, HCA II and rat CA II were found than in all other localizations. Our findings emphasize the importance of enzyme mediated bicarbonate/CO₂ removal from the feto-placental unit as opposed to simple bicarbonate diffusion or carrier mediated transport. As effective transfer routes should be considered not only umbilical cord — placental villi — intervillous space, but also fetal kidney — amnionic fluid — amnion — uterine vessels.     

Cholinesterases and arylesterase in the umbilical cord, the placenta, and the amniotic membrane, in the female at term]

Cholinesterasic activity of umbilical cord (tissue), completely bloodless, is exclusively due to pseudocholinesterase. Cholinesterase is more active in placenta than in cord; it is an acetylcholinesterase at 80 per cent. Both forms coexist, about equally, in amniotic membrane. A considerable arylesterasic activity is proved in cord, placenta and membrane, the greatest activity being in placenta. Comparing the greater activity in maternal plasma and cord blood's plasma to the very weak activity in amniotic fluid, it is possible to think that cork, membrane, placenta and also amniotic fluid pseudocholinesterase and arylesterase, come from plasma. On the contrary, placental acetylcholinesterase seems original and probably is the source of this enzyme activity in amniotic fluid.     

Comparison of Effect of Two Induction Doses of Methohexitone on Infants Delivered by Elective Caesarean Section

Observations were made on 26 infants delivered by elective caesarean section under general anaesthesia. A standard anaesthetic technique was employed using a methohexitone, relaxant, nitrous oxide-oxygen sequence with regulated ventilation and the administration of papaveretum after clamping the umbilical cord. In 12 patients the induction dose of methohexitone was 1·4mg/kg and in 14 it was reduced to 1·0 mg/kg. There were no significant differences between the two groups in the clinical status of the mothers, in operative technique and timing, or in the value of PO₂, PCO₂, and pH in the umbilical cord venous blood.The infants whose mothers received the lower dose of methohexitone were in better condition, as assessed by the number needing assisted ventilation, the time taken to establish regular respiration, the Apgar score, and the “Apgar minus colour” score.     

Selenium levels in related biological samples: human placenta, maternal and umbilical cord blood, hair and nails.

A study on selenium levels has been carried out in human placenta, maternal and umbilical cord blood, hair and nails of a group of 50 mothers and in the hair of the newborns. The determinations were perfomed by electrothermal atomic absorption spectrometry. The selenium concentration obtained for each sample type was as follows: For the human placenta the values obtained were between 0.56 and 1.06 microg/g (mean +/- standard deviation: 0.81 +/- 0.02 microg/g). The levels for the umbilical cord blood were 51.1-104.2 microg/l (76.3 +/- 6.5 microg/l). For the maternal blood the values measured were between 57.3 and 117.9 microg/l (90.0 +/- 15.2 microg/l), and for hair and nails were 0.22-1.5 microg/g (0.60 +/- 0.37 microg/g) and 0.46-1.57 microg/g (0.90 +/- 0.27 microg/g), respectively. For the hair of the newborns the values obtained were between 0.40 and 2.53 microg/g (1.04 +/- 0.48 microg/g). The effect of different variables as age, habitat, nutritional index or gestation age of the mothers on the selenium concentration in the samples was studied. The influence of the habitat is significant with a confidence level of 95% for the selenium concentration in maternal blood and umbilical cord blood samples. The influence of the mothers' age is significant with a confidence level of 95% for the selenium concentration in the umbilical cord blood samples. For the placenta samples, the effect of the nutritional index is significant with a confidence level of 95%. There is a positive correlation between samples of umbilical cord blood and the newborns' hair, between placenta and umbilical cord, and between cord blood and maternal blood.