The risk of hyperbilirubinemia in term neonates after placental transfusion - a randomized-blinded controlled trial.

OBJECTIVE: We aimed to demonstrate non-inferiority of delayed cord clamping (DCC) and cord milking (CM) in comparison to early cord clamping (ECC) in the incidence of hyperbilirubinemia requiring phototherapy. MATERIAL AND METHODS: 467 of maternal-foetal dyads were screened for eligibility. 389 term infants, of breastfeeding, non-smoking mothers were randomized to receive ECC ( < 40 s), DCC (1-2 min) or CM (4 times towards the neonate). The primary outcome was defined as hyperbilirubinemia requiring phototherapy. RESULTS: 307 patients were included in the analysis. CM did not increase the risk of phototherapy RR 11.27 95% CI (0.80; 2.04). Similar results were achieved when comparing DCC and ECC, RR 1.29 95% CI (0.82; 2.05). This was also true for CM vs DCC, RR 0.99 95% CI (0.64; 1.52). The prevalence of total serum bilirubin (TSB) at 24-48 hours was 10.8 mg/dL; 10.33 mg/dL and 11.39 in ECC, CM and DCC group respectively. Transcutaneous bilirubin (TcB) levels at 24-48 h were 7.58 mg/dL, 7.89 mg/dL and 7.60 mg/dL in the ECC, CM and DCC respectively. None of the neonates met exchange transfusion criteria or symptomatic polycythaemia. CONCLUSIONS: Our study suggests that placental transfusion is not associated with hyperbilirubinemia requiring phototherapy or exchange transfusion.

Implementing Delayed Umbilical Cord Clamping in Cesarean Birth Using a Novel Method: A Pilot Study of Feasibility and Safety.

INTRODUCTION: Although delayed cord clamping (DCC) is regarded as the standard of care for all vigorous newborns, those born via cesarean birth are less likely to be afforded this option, especially for longer than 30 to 60 seconds. This pilot study was undertaken to determine whether removal of the placenta before cord clamping to allow for DCC of at least 3 minutes during term, uncomplicated cesarean birth is feasible and without apparent safety issues in order to support a large prospective study on the benefits of this method. METHODS: Women having a term, uncomplicated cesarean birth who consented to the study were enrolled. Safety was assessed by comparing estimated maternal blood loss, newborn Apgar scores, temperatures, transcutaneous bilirubin levels, need for phototherapy, and neonatal intensive care unit admissions with a matched historical control group of women whose newborns had immediate cord clamping. Feasibility was measured by evaluating staff and maternal comfort with the intervention and by the ability to complete the protocol steps. RESULTS: Seventeen women consented to participate. The protocol was successfully completed in 94% of births. There were no differences in maternal and neonatal safety outcome measures between groups. There was high comfort level with the protocol among staff, and there was universal maternal satisfaction. DISCUSSION: This method of DCC in cesarean birth appears feasible and safe in this small pilot study and was associated with high maternal satisfaction and clinician comfort. Major organizations such as the American College of Nurse-Midwives and the World Health Organization have called for DCC of up to 3 to 5 minutes in all births, and this simple method has the potential to reach that goal in cesarean birth with minimal apparent risk. A large randomized controlled trial is warranted to determine the neonatal and maternal benefits and safety of this technique compared with a 30-to-60-second delay.

Effect of alternative positions of neonates prior to delayed cord clamping on placental transfusion: a randomized control trial.

Objective: To determine the effect of alternative positions (relative to placenta) of normal term neonates, prior to the recommended delayed cord clamping, on placental transfusion and short-term neonatal outcome.Methods: Normal term neonates born vaginally were randomly assigned to be placed either on mother's abdomen (Group AL, n = 97) or 20 cm below the introitus (Group BL, n = 102) for 90 seconds after delivery. Subsequently the cord was clamped. Outcome measures were anthropometry, hematological profile including ferritin at birth and at 3-4 months; and adverse effects, polycythemia, and jaundice.Results: Both groups had comparable outcome measures at birth. At 3-4 months, mean hemoglobin (AL: 12.0 ± 0.9 g/dl, BL: 12.3 ± 1.1 g/dl; p = .02, 95% CI: 0.03-0.58) and hematocrit (AL: 36.1 ± 2.7%, BL: 37 ± 3.2%; p = .01, 95% CI: 0.1-1.75) were significantly higher in BL group. Anthropometry, serum ferritin, incidence of anemia and iron deficiency at 3-4 months were similar in both groups. There was no significant difference in polycythemia, jaundice requiring phototherapy or respiratory distress between the two groups.Conclusions: Placing the baby below the placenta resulted in a statistically significant increase in hemoglobin and hematocrit at 3-4 months without any adverse outcomes. However, this meager quantum of increase did not translate into reduction of risk of anemia or improvement in iron stores.

The benefits of optimal cord clamping.

Optimal cord clamping is known and now widely recognised as having positive consequences for the neonate in the short- and medium-term. This review of some of the key literature published over the last five years on the effects of both ECC and OCC provides an insight into the evidence on this topic. The aim of this article is to summarise the key papers on the topic of the effect of timing of cord clamping, including some of those included in the Cochrane Review as well as the majority that have been published since, to provide an up-to-date overview.

Effect of Delayed Cord Clamping Above Versus Below the Perineum on Neonatal Hematocrit: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to determine if there is a difference in neonatal hematocrit at 24 hours of life in full-term newborns for which delayed cord clamping is performed above versus below the perineum. MATERIALS AND METHODS: One hundred one patients with singleton pregnancies >37 weeks of gestation presenting for delivery were randomized to delayed cord clamping above or below the perineum. At 24 hours of life, neonatal hematocrit was determined, and the difference was compared using statistical analysis. Secondary outcomes measured were need for phototherapy, transfusion, and neonatal intensive care unit (NICU) admission. RESULTS: Of 101 patients recruited for the study, 53 were randomized to the above group, and 48 were randomized to the below group. Twenty-seven patients in the above group and 26 patients in the below group completed the study. The above group had an average neonatal hematocrit of 52.7% (± 2.58%). The below group had an average neonatal hematocrit of 55.8% (± 2.42%). There was no statistical difference between groups (p = 0.10). Similarly, differences in secondary outcomes did not reach statistical significance. Three infants in the above group and one infant in the below group required phototherapy. None of the infants required blood transfusion. Three infants in the above group and one infant in the below group required NICU admission. CONCLUSIONS: When comparing delayed cord clamping above versus below the perineum, there is no difference in the neonatal hematocrit at 24 hours of life.

Optimal timing of umbilical cord clamping for term and preterm babies.

Deferring cord clamping allows blood flow between baby and placenta to continue for a few moments. This often leads to increased neonatal blood volume at birth. It also allows for longer transition to the neonatal circulation. Optimal timing for clamping the cord remains uncertain. This paper discusses the physiology of placental transfusion and presents the evidence from systematic reviews of randomised trials comparing alternative strategies for cord clamping for both term and preterm births. For healthy term infants, deferring cord clamping increases iron stores in infancy. Therefore, a more liberal approach to deferring cord clamping appears to be warranted, provided screening and treatment for jaundice requiring phototherapy is available. For preterm births, although there are few data on the main clinical outcomes, the evidence is promising that deferred cord clamping may be beneficial. For both term and preterm infants there is little information about long term development.

Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes.

BACKGROUND: Policies for timing of cord clamping vary, with early cord clamping generally carried out in the first 60 seconds after birth, whereas later cord clamping usually involves clamping the umbilical cord more than one minute after the birth or when cord pulsation has ceased. The benefits and potential harms of each policy are debated. OBJECTIVES: To determine the effects of early cord clamping compared with late cord clamping after birth on maternal and neonatal outcomes SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 February 2013). SELECTION CRITERIA: Randomised controlled trials comparing early and late cord clamping. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality and extracted data. MAIN RESULTS: We included 15 trials involving a total of 3911 women and infant pairs. We judged the trials to have an overall moderate risk of bias. Maternal outcomes: No studies in this review reported on maternal death or on severe maternal morbidity. There were no significant differences between early versus late cord clamping groups for the primary outcome of severe postpartum haemorrhage (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.65 to 1.65; five trials with data for 2066 women with a late clamping event rate (LCER) of ~3.5%, I(2) 0%) or for postpartum haemorrhage of 500 mL or more (RR 1.17 95% CI 0.94 to 1.44; five trials, 2260 women with a LCER of ~12%, I(2) 0%). There were no significant differences between subgroups depending on the use of uterotonic drugs. Mean blood loss was reported in only two trials with data for 1345 women, with no significant differences seen between groups; or for maternal haemoglobin values (mean difference (MD) -0.12 g/dL; 95% CI -0.30 to 0.06, I(2) 0%) at 24 to 72 hours after the birth in three trials. Neonatal outcomes: There were no significant differences between early and late clamping for the primary outcome of neonatal mortality (RR 0.37, 95% CI 0.04 to 3.41, two trials, 381 infants with a LCER of ~1%), or for most other neonatal morbidity outcomes, such as Apgar score less than seven at five minutes or admission to the special care nursery or neonatal intensive care unit. Mean birthweight was significantly higher in the late, compared with early, cord clamping (101 g increase 95% CI 45 to 157, random-effects model, 12 trials, 3139 infants, I(2) 62%). Fewer infants in the early cord clamping group required phototherapy for jaundice than in the late cord clamping group (RR 0.62, 95% CI 0.41 to 0.96, data from seven trials, 2324 infants with a LCER of 4.36%, I(2) 0%). Haemoglobin concentration in infants at 24 to 48 hours was significantly lower in the early cord clamping group (MD -1.49 g/dL, 95% CI -1.78 to -1.21; 884 infants, I(2) 59%). This difference in haemoglobin concentration was not seen at subsequent assessments. However, improvement in iron stores appeared to persist, with infants in the early cord clamping over twice as likely to be iron deficient at three to six months compared with infants whose cord clamping was delayed (RR 2.65 95% CI 1.04 to 6.73, five trials, 1152 infants, I(2) 82%). In the only trial to report longer-term neurodevelopmental outcomes so far, no overall differences between early and late clamping were seen for Ages and Stages Questionnaire scores. AUTHORS' CONCLUSIONS: A more liberal approach to delaying clamping of the umbilical cord in healthy term infants appears to be warranted, particularly in light of growing evidence that delayed cord clamping increases early haemoglobin concentrations and iron stores in infants. Delayed cord clamping is likely to be beneficial as long as access to treatment for jaundice requiring phototherapy is available.

Management of umbilical cord clamping.

The Royal College of Midwives (RCM) has updated its third stage of labour guidelines (RCM 2012) to be clearly supportive of a delay in umbilical cord clamping, although specific guidance on timing is yet to be announced. It is therefore imperative that both midwives and student midwives understand and are able to integrate delaying into their practice, as well as communicating to women the benefits; only in this way can we give women fully informed choices on this aspect of care. The main benefit of delayed cord clamping is the protection it can provide in reducing childhood anaemia, which is a major issue, especially in poorer countries. A review of the evidence found no risks linked to delayed clamping, and no evidence that it cannot be used in combination with the administration of uterotonic drugs. Delayed cord clamping can be especially beneficial for pre term and compromised babies.

Timing of umbilical cord clamping after birth for optimizing placental transfusion.

PURPOSE OF REVIEW: A brief delay in clamping the umbilical cord after birth offers health benefits to the newborn, with no adverse effects to the mother or her infant. Yet, in most obstetric practice, the cord is clamped soon after birth. A summary of the current evidence on delayed cord clamping and some reasons for the disconnect between the evidence and practice are discussed here, along with the recommendations from professional organizations and societies about this practice. RECENT FINDINGS: In term infants, umbilical cord clamping between 30 and 180 s after birth results in higher concentrations of hemoglobin and hematocrit during the neonatal period, and increased serum ferritin levels and a lower incidence of iron-deficiency anemia at 4-6 months of age. These are important benefits for children in low and middle income countries where iron-deficiency anemia is highly prevalent. In preterm infants, delayed cord clamping for at least 30 s increases the concentrations of hemoglobin and hematocrit, improves mean systemic blood pressure, urine output, and cardiac function, and decreases the need for vasopressors and blood transfusions during the neonatal period. It also decreases the prevalence of necrotizing enterocolitis, sepsis, and intraventricular hemorrhage (all grades). Milking of the unclamped umbilical cord toward the infant soon after birth also has similar beneficial effects. In some studies, more infants in the delayed cord clamping groups required phototherapy for jaundice. SUMMARY: Many professional organizations, societies, and experts recommend at least a 30-s delay before clamping the umbilical cord, especially after preterm births. The value of this practice for term births in resource-rich settings has not been evaluated.

Rethinking placental transfusion and cord clamping issues.

A brief delay in clamping the umbilical cord results in a placental transfusion that supplies the infant with a major source of iron during the first few months of life. Cord circulation continues for several minutes after birth and placental transfusion results in approximately 30% more blood volume. Gravity influences the amount of placental transfusion that an infant receives. Placing the infant skin-to-skin requires a longer delay of cord clamping (DCC) than current recommendations. Uterotonics are not contraindicated with DCC. Cord milking is a safe alternative to DCC when one must cut the cord prematurely. Recent randomized controlled trials demonstrate benefits for term and preterm infants from DCC. The belief that DCC causes hyperbilirubinemia or symptomatic polycythemia is unsupported by the available research. Delay of cord clamping substantively increases iron stores in early infancy. Inadequate iron stores in infancy may have an irreversible impact on the developing brain despite oral iron supplementation. Iron deficiency in infancy can lead to neurologic issues in older children including poor school performance, decreased cognitive abilities, and behavioral problems. The management of the umbilical cord in complex situations is inconsistent between birth settings. A change in practice requires collaboration between all types of providers who attend births.

Is there a role for autologous/placental red blood cell transfusions in the anemia of prematurity?

Because most extremely preterm infants with birth weight less than 1000 g need red blood cell transfusions, many attempts have been made to collect, process, and store placental blood (ie, umbilical cord blood) for autologous transfusions. Although it is feasible to do this, multiple problems in doing so including insufficient volumes collected, clotting, hemolysis, bacterial contamination, failure to significantly supplant need for allogeneic transfusions, and high costs have led many to question whether, on balance, autologous/placental red blood cell transfusion offers clinically significant benefits.

Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes.

BACKGROUND: Policies for timing of cord clamping vary, with early cord clamping generally carried out in the first 60 seconds after birth, whereas later cord clamping usually involves clamping the umbilical cord greater than one minute after the birth or when cord pulsation has ceased. OBJECTIVES: To determine the effects of different policies of timing of cord clamping at delivery of the placenta on maternal and neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2007). SELECTION CRITERIA: Randomised controlled trials comparing early and late cord clamping. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and quality and extracted data. MAIN RESULTS: We included 11 trials of 2989 mothers and their babies. No significant differences between early and late cord clamping were seen for postpartum haemorrhage or severe postpartum haemorrhage in any of the five trials (2236 women) which measured this outcome (relative risk (RR) for postpartum haemorrhage 500 mls or more 1.22, 95% confidence interval (CI) 0.96 to 1.55). For neonatal outcomes, our review showed both benefits and harms for late cord clamping. Following birth, there was a significant increase in infants needing phototherapy for jaundice (RR 0.59, 95% CI 0.38 to 0.92; five trials of 1762 infants) in the late compared with early clamping group. This was accompanied by significant increases in newborn haemoglobin levels in the late cord clamping group compared with early cord clamping (weighted mean difference 2.17 g/dL; 95% CI 0.28 to 4.06; three trials of 671 infants), although this effect did not persist past six months. Infant ferritin levels remained higher in the late clamping group than the early clamping group at six months. AUTHORS' CONCLUSIONS: One definition of active management includes directions to administer an uterotonic with birth of the anterior shoulder of the baby and to clamp the umbilical cord within 30-60 seconds of birth of the baby (which is not always feasible in practice). In this review delaying clamping of the cord for at least two to three minutes seems not to increase the risk of postpartum haemorrhage. In addition, late cord clamping can be advantageous for the infant by improving iron status which may be of clinical value particularly in infants where access to good nutrition is poor, although delaying clamping increases the risk of jaundice requiring phototherapy.

Ex vivo human placental transfer of the peptides pramlintide and exenatide (synthetic exendin-4).

Two peptides, pramlintide (37 amino acids), an analog of human amylin, and exenatide, synthetic exendin-4 (39 amino acids), are both in late-stage clinical development as potential new treatments for people with diabetes. Both are potential long-term treatments, and there is the likelihood that some women will become pregnant while using one of these peptide therapies. Therefore, it was important to evaluate the potential for each peptide to cross the placental barrier and thereby result in exposure to the fetus. This was examined using ex vivo perfusions of human placentas. The fetal and maternal side of a cotyledon were cannulated and perfused first with buffer, and then with radioactive antipyrine in order to establish the integrity of the system and the perfusion constants. Either pramlintide or exenatide was then added to each acceptable cotyledon perfusate on the maternal side. Each peptide was evaluated at an initial concentration near the therapeutic plasma concentration and at approximately 10-50 times that concentration in each of the three cotyledons. Maternal and fetal perfusate samples were assayed for peptide concentrations using an immunoassay. The ratio of fetal-to-maternal peptide concentrations during equilibrium perfusion were extremely low (pramlintide < or = 0.006, exenatide < or = 0.017). These data demonstrate negligible passage of either peptide across the placental barrier. It is, therefore, likely that maternal use of either peptide during gestation will result in negligible exposure to the fetus.