Placental Transfusion in the Newborn

KEY POINTS

1.

Delayed cord clamping (DCC) is a very powerful yet simple, no-cost intervention practice that can transform the lives of children and mothers around the world.
2.

DCC is a practice of waiting to cut the umbilical cord until sufficient time (3–5 minutes) has elapsed to permit blood flow from the placenta to the newborn while the baby is transitioning to extrauterine life.
3.

DCC facilitates placental transfusion and maintains systemic cardiac output until the newborn lungs establish lung circulation with the initiation of spontaneous breathing.
4.

Placental transfusion can also be accomplished by umbilical cord milking or cord milking through an intact umbilical cord.
5.

Placental transfusion volume to the newborn depends on the time to clamp the cord after birth, the position of the newborn relative to the location of the placenta, placental contractions, and the onset of spontaneous breathing in the newborn.
6.

DCC is an easily implemented intervention that requires joint cooperation among healthcare providers involved in childbirth and a participatory culture change in public health.
7.

Major benefits of DCC include improved cardiopulmonary transition, improved survival rates with reduced hospital mortality for preterm infants, reduction in iron-deficiency anemia in term infants during the first year of life through improved iron stores, and positive impact on neurodevelopment at 4 years of age.

Introduction

The transition from fetal to newborn life is characterized by both initiation of spontaneous breathing and changes to circulation. Delayed cord clamping (DCC) is a practice of waiting to cut the umbilical cord until sufficient time (3–5 minutes) has elapsed to permit blood flow from the placenta to the newborn while the baby is transitioning to extrauterine life. DCC facilitates placental transfusion, or the transfer of warm oxygenated blood from the placenta to the newborn at a slow rate, facilitated by uterine contraction. ^, DCC permits placental transfusion, and a passive transfer of stem cells, antibodies, and iron-rich blood from the placenta to the newborn occurs. DCC has enormous proven benefits for both premature and term infants. In the preterm infant, DCC assists with improved cardiopulmonary transition with stable blood pressures, reduction in intraventricular hemorrhages (IVH), reduced infection rates, reduced use of blood products in the neonatal intensive care unit, and improved survival rates. In the term infant, DCC is associated with reduction of both iron-deficiency anemia and improved neurodevelopmental outcomes at 4 years of age.

DCC is an age-old practice that has shifted to immediate clamping during the decades since the 1950s without conducting randomized controlled trials on this change. ^, Currently, the umbilical cord is clamped early, from immediately to within 15 seconds of birth, while there is still a significant circulation occurring through the umbilical vessels. The newborn is then quickly transferred to the pediatric provider in an effort to avoid delayed resuscitation. Immediate clamping of the cord is both a nonphysiologic and avoidable intervention that abruptly interrupts the natural process of placental transfusion. Immediate cord clamping prevents acquisition of adequate blood volume and thus may cause more harm than benefit to the baby. Reports from a systematic review and meta-analysis of delayed versus early umbilical cord clamping for preterm infants report a 28% to 30% increase in hospital deaths for preterm infants who had their cords clamped immediately after birth. ^,

It has been reported that 80 to 100 mL of blood transfers from the placenta in the first 3 minutes after birth. ^, ^, Clamping the umbilical cord while significant circulation is still occurring through the umbilical vessels drops the cardiac output by approximately 40%. This deprives the newborn of the benefit of added circulating blood volume (up to 100 mL) from continuing placental transfusion. Sick and preterm infants are especially likely to benefit from the additional blood volume achieved by DCC, besides term infants. ^, ^, Despite endorsements for DCC by numerous governing bodies and stakeholders ( Table 7.1 ) including the International Federation of Gynaecology and Obstetrics (2003), European Confederation of Midwives (2003), Society of Obstetricians and Gynaecologists of Canada (2009, 2016), International Liaison Committee on Resuscitation (2010, 2015), International Consensus on Cardiopulmonary Resuscitation (2011), World Health Organization (2014), National Institute for Health and Care Excellence (NICE) of the United Kingdom (2015), Royal College of Obstetricians and Gynaecologists (2016), Textbook of Neonatal Resuscitation , 7th edition (2016), Helping Babies Breathe, 2nd edition (2016), American Academy of Pediatrics (2017), American College of Obstetricians and Gynecologists (2017), and European Association of Perinatal Medicine, the practice of DCC has been slow to be adopted.

Table 7.1

Recommendations for Delayed Cord Clamping by Major Stakeholders

Organization	Preterm (<37 Weeks)	Term (>37 Weeks)
WHO (2014)	Delayed umbilical cord clamping (not earlier than 1 minute after birth) is recommended for improved maternal and infant health and nutrition outcomes
RCOG (2015)	Umbilical cord should not be clamped earlier than 1 minute if there are no concerns over cord integrity or the baby’s well-being	In healthy term babies, practice deferred cord clamping (delay clamping for at least 2 minutes)
ILCOR (2015)	For uncompromised babies, a delay in cord clamping of at least 1 minute from the complete delivery of the infant is recommended for term and preterm babies; as yet, there is insufficient evidence to recommend an appropriate time for clamping the cord in babies who require resuscitation at birth
ACOG (2017)	Delay umbilical cord clamping in vigorous term and preterm infants for at least 30–60 seconds after birth
AAP (2017)	Endorse recommendations of ACOG 2017
NICE (2019)	If a preterm baby needs to be moved away from the mother for resuscitation or there is significant maternal bleeding, consider milking the cord and clamp the cord as soon as possible; wait at least 30 seconds, but no longer than 3 minutes, before clamping the cord of preterm babies if the mother and baby are stable; position the baby at or below the level of the placenta before clamping the cord (2019)	Do not clamp the cord earlier than 1 minute from the birth of the baby unless there is concern about the integrity of the cord or the baby has a heart rate less than 60 bpm that is not getting faster; clamp the cord before 5 minutes to perform controlled cord traction as part of active management; if the woman requests that the cord is clamped and cut later than 5 minutes, support her in her choice (2015)
SOGC	Delayed cord clamping by at least 60 seconds is recommended irrespective of mode of delivery	The risk of jaundice is weighed against the physiologic benefits of delayed cord clamping

AAP, American Academy of Pediatrics; ACOG, American College of Obstetricians and Gynecologists; ILCOR, International Liaison Committee on Resuscitation; NICE, National Institute for Health and Care Excellence; RCOG, Royal College of Obstetricians and Gynaecologists; SOGC, Society of Obstetricians and Gynaecologists of Canada; WHO, World Health Organization.

Pathophysiology of Placental Transfusion

In the fetus, the lungs are filled with fluid. No gas exchange occurs, and this results in approximately 15% of the right ventricular cardiac output entering the fetal lungs. The oxygenated umbilical venous blood from the placenta that enters the right atrium is shunted across the foramen ovale to enter the left atrium. This serves as a preload for the left ventricle to supply oxygenated blood to the head and neck vessels. The umbilical venous blood that enters the right ventricle and pulmonary artery is then shunted across the ductus arteriosus to supply the rest of the body tissues. However, soon after birth, when the baby initiates breathing, the lungs are filled with air that assists with the drop in pulmonary vascular resistance and increases blood flowing into the pulmonary circulation. Thereafter, blood returns to the left ventricle to maintain systemic cardiac output. The newly accelerated pulmonary blood flow now replaces the umbilical venous blood as the source of the preload. This results in improved left ventricular output and systemic blood flow.

Clamping the umbilical cord resulted in a drop of right ventricular output and thereafter the systemic cardiac output in preterm lamb studies. If immediate clamping of the umbilical cord is performed before breathing is established, this blocks the acquisition of added blood volume from the placenta. This results in hypovolemia in a newborn, especially when compromised by asphyxia. Experimental studies in preterm lambs have shown positive effects for both systemic and cerebral hemodynamic parameters, including oxygen saturation when respiratory support is initiated prior to clamping the umbilical cord. The drop in right ventricular output is mitigated when the cord is clamped after breathing is established. The umbilical venous blood now serves as a source of left ventricular preload until the pulmonary venous return is established with breathing and systemic blood flow is thereafter maintained.

Thus establishing lung inflation and pulmonary circulation through effective breathing prior to the clamping of the umbilical cord could lead to smoother cardiovascular transition and reduce the risk of IVH. Therefore placental transfusion is an effective method of enhancing arterial oxygen content from the additional blood volume, maintaining cardiac output and increasing oxygen delivery during the transition period while the baby is attempting to establish breathing and pulmonary circulation. In addition, placental transfusion has been associated with lower incidences of sepsis and necrotizing enterocolitis in preterm infants. Placental blood remains an untapped physiologic reservoir of hematopoietic and pluripotent stem cell lines.

Factors That Determine Placental Transfusion

Several important factors determine the volume of residual placental blood that is transferred to the neonate ( Fig. 7.1 ). They are as follows.

Time of Cord Clamping

The volume of blood that is being transferred from the placenta to the infant is proportional to the timing of the cord clamping. DCC ranging from 30 seconds to the cessation of cord pulsations will transfer blood volumes ranging from 16 to 45 mL/kg ⁹ as opposed to immediate cord clamping in both vaginal and cesarean births.

Uterine Contractions

The mode of delivery (vaginal versus cesarean birth) influences the volume of placental transfusion. The uterine pressure gradient between the intrauterine umbilical vein and neonatal right atrium facilitates placental transfusion. In vaginal births, the uterine contractions during the third stage of labor can facilitate up to 50% of placental transfusion volume.

Source of Umbilical Blood Flow

The umbilical arteries constrict (usually within approximately 30–45 seconds), preventing a net backflow from the infant to the placenta. The umbilical vein remains patent during the third stage of labor and facilitates placental transfusion.

Time to Establishment of Spontaneous Breathing

Spontaneous breathing and crying result in lung aeration that establishes pulmonary circulation. Until spontaneous breathing is established, the umbilical venous blood serves as a source of left ventricular preload. Allowing babies to breathe with an intact umbilical cord that is still attached to the mother permits continued placental transfusion to the right atrium and subsequent left ventricular filling until the left ventricle blood is replaced with pulmonary blood flow. This allows a smooth cardiovascular transition from placental to neonatal circulation while mitigating wide swings of systemic and cerebral blood flow, especially in premature infants. ^,

The Effect of Gravity

The position of the infant influences the amount of placental transfusion volume through the effect of gravity. Placental transfusion occurs during DCC when infants are held below the level of the vaginal introitus in vaginal births or below the level of the uterine incision in cesarean deliveries. Term infants assigned to DCC for 5 minutes and placed on the mother’s abdomen received a larger placental transfusion volume compared with those with a 2-minute delay, as reported by Mercer et al. Mothers could safely be allowed to hold their baby on their abdomen or chest while blood continued to flow from the placenta to the newborn. ^, This practice enhances maternal–infant bonding.

Methods of Cord Management After Birth

Immediate Cord Clamping

Immediate cord clamping (ICC) refers to the clamping of the umbilical cord immediately, or usually within 15 seconds, after birth. ICC results in one-third of the total blood volume remaining in the placenta. ICC is still very common in hospital settings throughout the world. ICC deprives the infant of iron stores and contributes to iron deficiency in infancy. In fact, early umbilical cord clamping (less than 1 minute after birth) is not recommended by the World Health Organization unless the neonate is asphyxiated and needs to be moved immediately for resuscitation. ^,

Delayed Umbilical Cord Clamping

DCC is the practice of delaying the cutting of the umbilical cord until sufficient time has elapsed to permit placental transfusion to the infant. There is great variation in the timing of DCC, ranging from 30 seconds to 5 minutes to until the cord pulsations stop. The World Health Organization, International Liaison Committee on Resuscitation, and other organizations recommend waiting for at least 30 to 60 seconds after birth for the most vigorous term and preterm newborns. ^, This practice facilitates a physiologic passive transfer of warm, oxygenated, iron-rich blood from the placenta at a slow rate to the newborn. DCC prevent iron-deficiency anemia during the first 6 months of life. It also reduces anemia at 8 and 12 months of age in high-risk populations.

Intact Umbilical Cord Milking

DCC should not be confused with umbilical cord milking (UCM). Milking refers to the manual expression of blood from the umbilical cord. Intact UCM is the active practice of gently squeezing or milking blood down a short segment of intact umbilical cord (20–30 cm) that is attached to the placenta toward the baby 3 to 4 times at a rate of 10 cm/sec before clamping the cord. UCM is another method of transfusing placental blood to the newborn that is not physiologic but contributes to added neonatal blood volume. UCM offers the added benefit of not delaying resuscitation in an unstable and compromised neonate who needs to be timely resuscitated. UCM can be performed in any setting in 15 to 20 seconds, equivalent to the time it takes for ICC. Thus UCM may serve as an alternative to DCC by providing equivalent benefits to preterm infants but without delaying resuscitation. In a post hoc analysis of a prematurely terminated randomized clinical trial of UCM versus DCC for 45 to 60 seconds among preterm infants born at <32 weeks of gestation, there was a statistically significant higher rate of severe IVH in the UCM subgroup in infants born at <28 weeks of gestation that led to early study termination for this age group. Retrospective analysis of extremely preterm infants (<29 weeks of gestation) from the National Institute of Child Health and Human Development Neonatal Research Network suggests that DCC is the preferred practice for placental transfusion, because UCM exposure was associated with an increase in the adverse outcome of severe IVH (grade 3 or 4). Three other randomized clinical trials comparing DCC for 30 to 60 seconds with UCM performed four times did not show a significant difference for rates of IVH in preterm infants born at <33 weeks of gestation. Effects on reducing mortality in preterm infants are similar to those reported for DCC. Intact UCM is considered an alternative method for providing placental transfusion if DCC is not feasible in term infants.

Cut Umbilical Cord Milking

Cut UCM is the practice of actively squeezing the residual blood down a long segment of an umbilical cord that is cut soon after birth and detached from the mother but still attached to the baby. The neonatal provider subsequently milks the blood into the baby after untwisting the long segment of the cord.