INTRODUCTION
Placental transfusion is defined as the transfer of residual blood from the placenta to the newborn (NB) in the first minutes of life, a physiological mechanism that plays a short- and long-term essential role in the child's health1.
Among the recommendations based on scientific evidence for birth assistance that favor placental transfusion, the delayed cord clamping (DCC) stands out2. DCC is defined as application of a clamp to the cord >30 seconds after birth or based on physiologic parameters (such as when cord pulsation has ceased or breathing has been initiated), without cord milking. The time of DCC can range between 30 and 180 seconds, with a delay of 30 to 60 seconds®.
DCC offers several benefits to the newborn when compared to the immediate cord clamping (ICC), defined as application of a clamp to the cord <30 seconds after birth, without cord milking3, including: greater serum ferritin levels4, increased hemoglobin after birth3, additional transfer of 15-30 ml/kg blood volume4, transfer of immunoglobulins and essential stem cells to the tissues and repair of the neonate's organs(2, 5). Furthermore, in premature NBs, DCC is associated with significant benefits, such as less need for blood transfusion, reduced incidence of necrotizing enterocolitis and intraventricular hemorrhage2.
Another form of placental transfusion that has been studied and discussed today is umbilical cord milking (UCM). There are two types of UCM, namely: intact-UCM (I-UCM) (also referred to as "stripping" or just UCM), defined as repeated compression of the cord from the placental side toward the infant with the connection to the placenta intact at any time point within the first few minutes after birth; and cut-UCM (C-UCM) (also referred to as "stripping"), defined as drainage of the cord by compression from the cut end toward the infant after clamping and cutting a long segment3.
The I-UCM, consists of holding the umbilical cord gently and sliding the index finger and thumb on the umbilical cord, at 20 cm from the base of the newborn's navel, with the objective to carry the residual placenta blood present in the cord towards the newborn. Generally, milking is repeated three to four times, but one must wait on average 2 seconds between milking, so the umbilical cord is refilled with blood before being milked again2.
Another way to do this procedure is the C-UCM, which consists of cutting and clamping 25 cm from the umbilicus immediately after birth; the baby is delivered to the pediatric team and positioned on the radiant warmer, then, the cord is lifted and milked from the end of the cut to the navel, promoting the emptying of all its content towards the newborn6. UCM allows a faster placental transfusion7.
It should be noted that often the newborn needs placental transfusion, since it facilitates the neonatal transition/adaptation and the recovery of their health, so UCM can be a viable alternative when there is an impediment to perform the DCC. That is why it is important to have a produced knowledge map about this subject, with the benefits and potential risks well elucidated to guide the practice of nurses and midwives based on current evidence. Thus, these professionals will have accurate information about this technique in order to ensure the best obstetric practices. In this perspective, this study aimed to map the available evidence on UCM in newborns.
MATERIAL AND METHODS
This is a scope review based on the protocol proposed by the Joanna Briggs Institute8, developed from the following steps: elaboration of the research question; identification of relevant studies, selection of studies; data mapping; separa tion, summarization and reporting of results; and communicating results. The report of this review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines®.
To guide the research, the question 'What is the knowledge produced on the umbilical cord milking by international literature?' was formulated, based on the patient, concept, and context (PCC)8, defining: P - newborn/infant; C - umbilical cord milking; C - birth.
The articles were searched by people with previous experience in this type of research in the nursing area in the following databases: Medical Literature Analysis and Retrieval System Online (MEDLINE), SciVerse Scopus (SCOPUS), Cumulative Index to nursing and allied health literature databases (CINAHL) and Web of Science (WOS). The search was carried out using the controlled descriptors [Descriptores en Ciencias de la Salud (DeCS), Medical Subject Headings (MeSH) and CINAHL Heading], and uncontrolled (keywords), namely: infant, newborn, umbilical cord milking, placental transfusion and umbilical cord blood. The crossings were performed with the Boolean operators AND and OR.
The first study search process was carried out in October and November of 2019. In February 2022, an update of the search was carried out with studies published between November 2019 and February 2022. The research was carried out by two independent researchers, in order to identify the differences in the findings and include as many studies as possible. Subsequently, the identified articles were compared and, in case of disagreement, sent to a third researcher for a consensus.
The selection of studies was based on the following inclusion criteria: original articles, in English, Spanish or Portuguese, no publishing time limits. We chose not to limit the time to know more comprehensively everything that has already been produced on the theme. Review articles, repeated articles, which were not found in full and did not answer the guiding question, were excluded. The search engine and the number of articles collected in the different databases are shown in Table 1.
The reference list of included articles was also consulted to identify additional publications that had not been mapped. The full text was read to assess its eligibility and, then, 18 articles were included. The search flowchart is shown in Figure 1, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart®.
After the selection, the publications were mapped and an analytical table was created containing the characterization data of those included in this review. This data charting form was based on the Joanna Briggs Institute manual for scoping reviews8.
The data's were extracted and mapped descriptively8. Some results were presented in the word cloud format. The word cloud groups and organizes the words graphically depending on their frequency. It is a simpler lexical analysis, however, graphically quite interesting, as it enables the rapid identification of keywords of a corpus9. In this sense, the word cloud was used to synthesize the main information found in the studies, interpreting them to describe the available evidence that answered the study question.
As this is a scoping review, according to the adopted methodology, the methodological quality assessment of the included studies is waived. To ensure ethical aspects, the reliability and the fidelity of the information found in the selected publications were guaranteed through appropriate referencing and rigor in the presentation of the findings.
RESULTS
It included 73 articles, 55 of which were identified in the databases and 18 from their references, published in English between the years 1949 and 2022. Most publications are randomized controlled trials (RCT) (49; 67.12%), conducted in the United States of America (USA) (26; 35.61%) and in India (13; 17.80%). As for the authors' degree, most medical authors were pediatricians and neonatologists (47; 64.38%), few were obstetricians and gynecologists (24; 32.87%) and only two nurses (Table 2). Most of the studies found performed a comparison between UCM and ICC, focusing on preterm newborns (PTNB).
The UCM has been part of the practice of few professionals who care for the newborn64,67,73. However, the protocol for carrying it out varied among the included studies, in some of them the infant was placed on sterile drape at or below the level of the placenta (between the mother’s thighs in vaginal delivery or to the mother’s side in cesarean delivery)(12,14,18-24,27,29-36,39-41,42,43,45-49,53,58, 66,69,74,76-78)
For neonates that underwent I-UCM, the cord was pinched as close to the placenta as possible with the thumb and index fingers of the left hand and about 30 cm of the umbilical cord was vigorously milked towards the umbilicus. Speed of milking was approximately 5 or 10 cm/s each within the initial 5 min of life. The cord was then released at the placental end and allowed to refill with blood for a brief 1 to 3 seconds pause between each milking motion12,14,18-24,27,29-36,39-41,42,43,45-49,53,58,66,69,74,76-78. In general, the entire procedure was completed in not more than 30 s. After this, the umbilical cord was clamped and cut at 2-3 cm from the umbilicus and the infant taken to the warmer for routine newborn care20,23,26,35,43,48,50,61,69,74,77.
In cases of C-UCM, the 20-30 cm length of umbilical cord was clamped and cut (within 10 s), and then milked15,17,25,26,28,44,59. Concerning the number of times that cord milking was performed, it varied between one to eight, but in most studies, it was performed three times 12,13,16-21,25-30,32-34,36,39-41,43-45,46-49,52,53,57-59,63,65,66,70,74,76,80.
Also was found comparisons between the types of milking C-UCM and I-UCM29,43,57,78. Other studies performed other types of comparison, such as: UCM x 'non-milking'34,40, ICC x DCC x UCM71 and UCM x DCC x DCC with UCM25,79.
The main benefits of UCM compared with ICC in preterm neonates are described in Figure 2. However, other studies have compared UCM with ICC in term newborns (TNB), whose main benefits of UCM are shown in Figure 3. Another type of comparison found in the articles was between DCC and UCM, and the results show that there are no differences between the two procedures as described in Figure 4.
In addition the UCM was analyzed in a study that evaluated the neonates requiring resuscitation39, infants with acidosis at birth6 and with depressed at birth42. Most studies have not found adverse events resulting from UCM. However, the existing adverse event appears to be the same as that of DCC: higher incidence of hyperbilirubinemia requires phototherapy30. In PTNB, some publications evidenced a lower number of neutrophils in the groups submitted to UCM compared to the DCC group31,41. Also in PTNB studies found that there was an increased incidence of severe intraventricular hemorrhage in infants who received UCM compared with DCC 45,56,58. However, research has found that there was a significant reduction in the incidence of intraventricular hemorrhage in the UCM group as compared to the ICC group 18,47,53,56.
DISCUSSION
This mapping allowed us to know how UCM has been performed in obstetric practice and its benefits and risks for the neonate, mainly compared to the ICC and the DCC. Most of the publications are results of RCT aiming to prove the advantages of UCM and providing evidence for its use. Through this review, it was possible to verify that UCM is more beneficial to neonates than ICC and that it can be used as an alternative to DCC, since it is a quick method to obtain placental transfusion to the newborn, as it is usually performed in less than 30 seconds the entire procedure.
About the use of UCM in the assistance to the NB, it was identified that a few professionals have used this technique. A survey conducted with neonatologists in the USA64 and a study with obstetricians' practices in Turkey73, identified that more than half of them do not perform UCM. This also was found in a research with nurse-midwives67. These results indicate that evidence related to this practice should be widely disseminated among these professionals in order for neonates to benefit from this practice.
An important aspect to highlight from the analysis of the publications is that there is no standardization in the protocol used in the milking.
The vast majority share the same position of the infant at or below the level of the placenta, the milking of about 30 cm of the cord towards the navel in approximately 5 or 10 cm/s each, and the conclusion in not more than 30 s.
About the technique, some studies used the intact milking technique and others, the cut. Researchers, when comparing the cut with the intact milking, identified that the average blood volume of the intact UCM was higher than in the cut. Despite being a pilot study, with a small sample and without randomization, clinical benefits are important, however further studies are needed to compare these two techniques for further clarification. Although milking the cut umbilical cord may allow a faster onset of resuscitation in the newborn, the smaller total amount of transfused blood volume compared to intact milking raises questions about the general benefits of cut UCM43.
However, other studies have identified that there were no significant differences in terms of mean gestational age, birth weight, Apgar scores at the 5th min, first breathing time, arterial oxygen saturation, cerebral regional oxygen saturation, blood pressure, hemoglobin levels, and residual placental blood volume78 hemoglobin/hematocrit, peak bilirubin values, the incidence of intraventricular hemorrhage, need for blood transfusion, and the use of pressors57 between C-UCM and I-UCM groups.
Another aspect related to the milking technique is the number of times that must be performed, which is not yet standardized. In this review, most studies performed three times; however, more studies are necessary to clarify this issue. A study found no differences between the milking of the cut cord performed once, with the milking of the cord intact performed three times, since both groups showed similar benefits such as probability of not needing transfusion during hospitalization and number of administrations of red blood cell transfusion in the first 21 min of life. Although this study has some limitations, such as a small sample size not being a prospective randomized study, it demonstrated that the cutting of UCM performed only once seems to be a less demanding and easier method to be performed29.
Other comparisons were made between the types of milking. A study compare UCM x 'non-milking', demonstrated benefits in the neurological development of newborns submitted to milking34,40. Others that compared ICC x DCC x UCM, finding higher levels of hemoglobin and hematocrit in the last two groups71, and greater oxidative stress13, higher mortality or major morbidity56, lower 5-minute Apgar's score in those submitted to ICC. Also was identified that there were no significant differences between groups for measures of electroencephalogram activity or cerebral near infrared spectroscopy52, total oxidant capacity, oxidative stress index, and peroxynitrite measurements81.
Still in relation to the type of milking, the technique of milking after DCC has been used, such as a study carried out with TNB, which compared this procedure with DCC and with milking separately and demonstrated that the iron reserve in this group was significantly higher than in the other two. Cord milking after DCC can increase the volume of extra blood that remains in the non-pulsatile cord, in addition to the usual placental transfusion and, thus, improve hematological parameters in the newborn. Despite these results, further studies are needed to better elucidate these findings25.
Among the benefits of UCM, when compared to ICC, there is an increase in the levels of Hemoglobin, Hematocrit and Serum Ferritin, according to the articles analyzed11-13,17,19,35,41. Placental transfusion contributes to 30 mL/kg of blood to the neonate, in extremely preterm infants with ICC about one-half of their normal circulating in utero blood volume are left in the placenta83. The increase in these levels helps prevent childhood anemia1. This is important for the PTNB, which is a population at risk for anemia, especially the small for gestational age and extremely low birth weight infants83. In this sense, the ICC can be one of the probable causes for anemia in preterm infants, as it deprives them of blood from the placenta.
In more recent studies included in this review, which compared UCM to DCC in TNB and PTNB, similar levels of hemoglobin, hematocrit and serum ferritin were found between the two groups14,27,33,65. It should be noted that, at term birth, the newborn has an iron reserve of 75 mg/ kg and, when submitted to DCC, an additional 40 mg occurs in one minute and 50 mg in three minutes. This means an iron reserve of 115-125 mg/kg, which is sufficient to prevent iron deficiency between the fifth and twelfth month of life1.
Some analyzed publications24,38,55 demonstrated that the newborns submitted to UCM had higher levels of serum hemoglobin, hematocrit and Ferritin when compared to those in which DCC was performed. This can be explained because some factors may influence the amount and speed of placental transfusion at DCC, such as the time of clamping of the umbilical cord, uterine contractions, umbilical blood flow, beginning of breaths and the positioning of the newborn after birth84.
Especially in low and middle income countries, whose population is deficient in food and has a higher prevalence of anemia, the placental transfusion, whether by DCC or UCM procedure is advantageous and may have clinical value, since it reduces the incidence of neonatal and childhood anemia85. Considering that, in some studies24,38,55, UCM presented higher levels of hemoglobin and hematocrit when compared to DCC, it is deduced that this procedure may also reduce the incidence of neonatal and childhood anemia.
The studies analyzed also showed that the NB submitted to milking compared to the ICC technique had higher mean arterial pressure levels13,17,20 and that, in PTNBs, UCM was associated with higher blood pressure in 15 hours of life when compared to DCC24. It is noted that in term newborns, this increase may not be clinically significant, but in hypotensive neonates, the gain of 4 mmHg derived from circulatory blood by placental transfusion may be sufficient to prevent hypovolemia13,17.
This research also showed that there is no difference in the average number of transfusions in the first 42 days of life between PTNBs submitted to UCM and DCC13 and that UCM reduced the need for blood transfusion when compared to ICC 7,20,34. Placental transfusion promotes autotransfusion of the volume of residual blood volume in placenta available to the newborn. Already the ICC don't allow it, so it can contribute to the loss of organ-specific vascular competence in the lung, gastrointestinal tract, brain, kidney, and other organs83.
As well, UCM contributes to the growth of the newborn (weight, height and average arm circumference) and does not impair the neurological development in the long run32. Infants undergoing UCM showed higher language and cognitive scores compared to those undergoing DCC44. The child's largest iron reserve, offered through UCM or DCC, certainly contributes to child development, since the iron-deficiency anemia in infants affects neuro-cognitive functions of learning and memory which can result in fatigue and low economic productivity83.
It was also observed that UCM helps reduce morbidities due to prematurity such as intraventricular hemorrhage and necrotizing enterocolitis, compared to ICC in PTNB, in the publications covered in this review18,20. Such benefit may be due to the considerable amount of umbilical cord blood stem cells received through placental transfusion5.
According to the selected studies, UCM is a procedure that reduces the need for respiratory support in premature infants. In addition, it reduces the time of mechanical ventilation and the use of supplemental oxygen in PTNBs, compared to those who underwent DCC12,19. This result may also be associated with the placental blood that is a rich source of fetal stem cells84.
Stem cells play a fundamental role in the development and maturation of various organs and systems, mainly in the central nervous, respiratory, endocrine, immune and hematological systems. Moreover, they are involved in anti-inflammatory and anti-infectious actions, reducing the appearance of several diseases, including anemia of prematurity, intraventricular hemorrhage, sepsis and periventricular leukomalacia, in addition to reducing complications in respiratory distress syndrome. They also seem to have a beneficial effect on chronic lung diseases, apnea of prematurity, retinopathy of prematurity and necrotizing enterocolitis5.
Another factor associated with the reduced morbidities due to prematurity identified in this research was the better cerebral13 and systemic16) oxygenation provided by the greater blood flow promoted by milking. A study carried out in PTNB randomized to UCM had greater measures of superior vena cava flow and right ventricular outlet in the first 6 h and 30 h of life19. In very low birth weight infants (<29 weeks, birth weight <1250g), milking provided stabilization of oxygenation and cerebral perfusion by increasing the left ventricular diastolic function by increasing the left ventricular preload16.
If the umbilical cord is cut before the start of spontaneous breaths, it can negatively affect cerebral perfusion during the transition from the fetal to the neonatal period. This is probably due to the increased afterload observed in the left ventricle and the decreased preload provided by the umbilical vein. Air entering the newborn's lungs increases the pulmonary blood flow, which provides most of the preload for the left ventricle. In this sense, hemodynamic stabilization after delivery, which allows the maintenance of cerebral blood flow, is particularly important to preserve the vascular germinal matrix and reduce severe intraventricular hemorrhages in the newborn84.
One of the studies examined showed differences in systemic blood flow between newborns and preterm infants, and preterm infants born through cesarean delivery and submitted to UCM had greater flow from the superior vena cava and ventricular outflow in the first 12 hours of life, showing higher systemic blood flow than in those in which the DCC was performed24. However, a study carried out with TNB showed that UCM was similar to DCC in terms of blood flow speed and Doppler indices in the middle cerebral artery27.
In addition, another study demonstrated that PTNBs submitted to UCM have a higher heart rate and oxygen saturation and require smaller amounts of oxygen after delivery when compared to babies undergoing ICC. In this sense, it can be said that blood transfusion provided by both DCC and UCM improves pulmonary blood flow and helps with lung expansion19.
The transition from fetus to neonate is a physiological process that includes numerous adaptations in their organ systems. There is a sudden transition to air breathing that involves complex changes in pressure, circulatory system and pulmonary blood flow. To facilitate this adaptation, adequate blood volume is necessary to ensure full perfusion to all of the infant's organs in adapting to extra-uterine life83.
When compared to ICC, UCM reduces the need for support immediately after delivery and in situations where resuscitation was needed immediately, milking has the advantage of being completed in a very short period of time to improve stability after delivery1. Thus, it can be indicated in situations where the NB requires resuscitation immediately at birth to provide placental transfusion.
About resuscitation, the studies showed that UCM practice has benefits for newborns. One of the studies evaluated premature infants who needed resuscitation and found that UCM provides better cardiovascular results during the neonatal transition and better stabilization of blood pressure than in those submitted to ICC39. In cases of neonates with acidosis at birth, those who received UCM required less resuscitation and continuous respiratory support6. Furthermore, UCM is extremely beneficial for newborns and late preterm infants (≥35 weeks) who are born depressed. It was assessed that milking does not delay neonatal resuscitation or resuscitation efforts, compared to those who received ICC42.
During neonatal resuscitation in term and late preterm infants, UCM can prevent or reduce brain damage, since, when performing this procedure, there is an increase in intravascular volume, cerebral blood flow and oxygen supply43. In this sense, this intervention can be valuable, especially in places with scarce resources, where there is no access to technological support and unavailability of blood components6.
Regarding oxidative stress, the comparison between the three umbilical cord management procedures (ICC, DCC and UCM) detected that the ICC increases the production of disulfide titers and decreases the thiol levels in the newborn. Low plasma thiol levels and increased disulfide levels may be indicative of oxidative stress, which would contraindicate the performance of this procedure in newborns34.
As for the adverse events resulting from the UCM, these seem to be the same as the DCC, which is the increased incidence of hyperbilirubinemia in neonates requiring phototherapy. However, as some studies have not found this outcome, it is necessary further research is needed for clarification. Despite the increased risk of jaundice, the benefits associated with UCM outweigh it. In this sense, professionals who provide assistance to the NB must guarantee the use of strategies to monitor and treat neonatal jaundice86.
In premature newborns, in some studies, lower numbers of neutrophils in the groups submitted to UCM compared to the DCC group. However, neutropenia is an expected event in newborns submitted to umbilical cord blood transfusion and can be explained by the delayed recovery of neutrophils in these situations31,41.
Another adverse event reported was severe intraventricular hemorrhage, in PTNB. This outcome can be justified because extremely premature newborns do not have adequate self-regulation of the brain system compared to more mature neonates. Due to this system immaturity, changes in the systemic blood flow obtained with the UCM can be transferred to the cerebral blood flow causing rupture of the vessels87. In addition, in extreme preterm newborns, the maternal condition of chorioamnionitis releases inflammatory mediators that cross the blood-brain barrier, promoting a neuroinflammatory cascade, which increases the fragility of the germinal matrix and the cerebral blood vessels46.
Although there is evidence on the reduction of intraventricular hemorrhage in preterm neonates submitted to late cutting of the umbilical cord, there are few studies on the UCM as an alternative to decrease intraventricular hemorrhage in extremely low birth weight newborns. In this sense, further studies on the safety and efficacy of UCM are needed as an approach for performing placental transfusion in these neonates87.
Given all that has been presented, it can be said that UCM is a proven safe intervention that guarantees adequate placental transfusion at birth for TNB and PTNB, with several benefits well described in the literature24.
Because it is a scope review, the studies included in that review have not been formally assessed for methodological quality. In this sense, despite the inclusion of a range of studies, which allowed us to know the nuances of UCM, care should be taken as to the incorporation of the interventions described in the studies in clinical practice.
CONCLUSION
Through this scoping review, it was possible to map the available evidence on UCM in newborns to support birth care. Most of the studies evidenced the benefits of using UCM instead of ICC, or as an alternative to DCC, in situations where rapid placental transfusion is required. The superior benefits to the ICC evidenced were: higher levels of Hemoglobin, Hematocrit and Serum Ferritin, and reduction of complications in preterm newborns, such as the need of blood transfusion. When compared to DCC, it has similar benefits; however, UCM is considered a faster method of placental blood transfusion. Therefore, it can be an alternative when delayed cord clamping cannot be performed.
In addition, this study enabled the identification of gaps that still need to be investigated on UCM, such as the number of times milking should be performed, what is the best type of milking and long-term results.