|Year : 2020 | Volume
| Issue : 2 | Page : 45-54
Functional echocardiographic evaluation of the effect of placental transfusion in full-term newborns who need resuscitation
Magdy Badereldin, Aly AbdelMohsen, Asmaa Emad, Adham A Badib
Department of Paediatrics, Alexandria University, Alexandria, Egypt
|Date of Submission||20-Feb-2020|
|Date of Acceptance||11-Apr-2020|
|Date of Web Publication||5-Oct-2020|
MD Adham A Badib
Lecturer in Pediatrics and Neonatology, Alexadria Universiety Faculty of Medidcne, 35 Sultan Hussien Alexandria; Department of Pediatrics, Alexandria University, Alexandria, 21131
Source of Support: None, Conflict of Interest: None
Background At the time of delivery, newborn babies have to pass through transitional changes in many of their life supporting systems. A more successful transition at the level of the cardiovascular system, hence an overall better transition, could be reached if placental transfusion is implicated.
Aim To study the feasibility of doing intact umbilical cord milking (I-UCM) as a method of placental transfusion in term neonates who were born depressed and needed resuscitation and to study its hemodynamic effects using echocardiography.
Patients and methods A randomized controlled study involving 66 patients over a period of 6 months was conducted. The studied population was assigned to receiving I-UCM or immediate cord clamping. Laboratory parameters, resuscitation interventions, and finally, functional echocardiographic were studied in both groups.
Results It was feasible to perform I-UCM in the delivered babies in the assigned group. Such group was found to have faster time for the first breath (45 vs. 60 s), higher Apgar score (5, 8, 10 vs. 4, 7, 9), and no need for more advanced resuscitation interventions compared with the group with immediate cord clamping. Higher levels of hemoglobin (17.20 vs. 15.85) were noticed with less need to transfusion in the intervention group. Better echocardiographic assessments were shown regarding ejection fraction, tricuspid annular plane systolic excursion, and lower incidence of pulmonary hypertension in the I-UCM group (70 vs. 66%, 1.02 vs. 0.87 cm, and 33.3 vs. 62.5%, respectively).
Conclusions The practicality of UCM was easy and feasible in both depressed and nondepressed newborns. UCM as a method for placental does not affect resuscitative measures and results in better cardiac performance in asphyxiated babies.
Keywords: cord milking, functional echocardiography, perinatal depression, placental transfusion
|How to cite this article:|
Badereldin M, AbdelMohsen A, Emad A, Badib AA. Functional echocardiographic evaluation of the effect of placental transfusion in full-term newborns who need resuscitation. Alex J Pediatr 2020;33:45-54
|How to cite this URL:|
Badereldin M, AbdelMohsen A, Emad A, Badib AA. Functional echocardiographic evaluation of the effect of placental transfusion in full-term newborns who need resuscitation. Alex J Pediatr [serial online] 2020 [cited 2020 Oct 20];33:45-54. Available from: http://www.ajp.eg.net/text.asp?2020/33/2/45/297239
| Introduction|| |
The number of newborn babies needing advanced resuscitative intervention methods at the time of delivery is ∼10–15%; such percentage places neonatal resuscitation as the most frequently performed resuscitation in medical practice .
Historically, the major concern at the time of delivery was ventilation and adequate oxygenation, although appropriate cardiovascular transition which is temporally related to umbilical cord clamping, is of utmost importance as it establishes pulmonary perfusion that is cornerstone for effective ventilation .
Placental transfusion is defined as the amount of blood transferred from the placenta to the neonate during the first few minutes of age. Regarding the amount of such blood, it is to be noted that at midgestation, placenta accommodates two-thirds of fetoplacental blood volume, with advancing gestational age, two-thirds are found in the fetus and the placenta keeps up to one-third ,. Immediate cord clamping (ICC) will decrease the left ventricular preload , such decreased preload when combined with abrupt elevation of the systemic vascular resistance as a result of removal of the placenta will end in drop in cardiac output, bradycardia, and alteration in cerebral circulation . On the contrary, delayed cord clamping would allow transfusion of a significant blood volume retained in the placenta reaching up to 25 ml/kg, with subsequent increase blood pressure, better delivery of RBCS to the organs, and good tissue prefusion .
Umbilical cord milking (UCM) is suggested to be effective as a means of placental transfusion , in addition to its practicality, where it takes about 20 s to be done, allowing the immediate start of resuscitation maneuvers .
Hemodynamic assessments via clinical parameters are widely used but have limitations in asphyxiated babies, with variable systemic vascular resistance and poor cardiac output . Thus, echocardiographic evaluations in babies receiving intensive medical care seem mandatory to aid in evaluation and management. Functional echocardiography is different from echocardiography performed by a pediatric cardiologist, where the main focus is to provide a consultative, cross-sectional, high-end opinion regarding structural heart and an assessment of the function at the time of the measurement .
| Patients and methods|| |
The study was conducted at both the delivery room and operation room in the Alexandria University Maternity Hospital and indeed the Alexandria University Neonatal Intensive Care Unit, a 70-incubator capacity level-three unit with an annual admission of ∼1500 babies.
This was a randomized, nonblinded, controlled clinical trial. All full-term newborn infants who fulfilled the eligibility criteria having risk factors for perinatal hypoxia such as emergency cesarean section, assisted delivery, uterine rupture, cord prolapse, abnormal fetal heart tracing, and shoulder dystocia delivered at Alexandria Maternity Hospital during the study period, from March 2018 till the end of August 2018, were included in the study. All of them received resuscitation according to NRP 2017 guidelines. Babies with major congenital anomalies, those with suspected intracranial hemorrhage, monochorionic twins, abruption of the placenta, and retroplacental hematoma were excluded.
It was not feasible to randomize infants before they were born, as it cannot be accurately predicted which infant will be depressed at birth. There is also no time to randomize infants after they are born, as the intervention (UCM) must be done immediately after birth. We choose to randomize neonates based on their months of birth. Infants born during the first 3 months of the study period (March, April, and May) were included in the UCM group and those born during the next 3 months (June, July, and August) were assigned in the control group.
Assessment of the feasibility of the intervention and evaluation of the outcome was done only for those who were admitted to the neonatal intensive care unit (NICU) at Alexandria University Children’s Hospital.
Intervention and data collection
All studied neonates had full maternal and obstetrical history taken, received resuscitation in the delivery room according to NRP 2017, and had their hemodynamic parameters recorded: heart rate, blood pressure, oxygen saturation, and fraction of inspired oxygen (FiO2).
- Those subjected to the intervention: UCM was performed by holding the newborn mostly at or ∼20 cm below the level of the placenta. The cord was pinched as close to the placenta as possible and milked toward the infant over a 2-s duration. The cord was then released and allowed to refill with blood for a brief 1- to 2-s pause between each milking motion. This was repeated for three to five times. After completion, the cord was clamped, and the newborn was handed to the resuscitation team ,. Using the wall-mounted clock in the delivery room, the neonatal fellow attending the delivery recorded the time elapsed from when the infant was delivered until the time the umbilical cord was clamped by the obstetrician in both groups of the study.
- Echocardiographic evaluation: two echocardiographic examinations were performed for all neonates in the two groups at 6–12 h and at 24–36 h of life. Using an echocardiographic machine: PHILIPS model no. HDX11 XE and a probe with a frequency range 3–8 Hz, we assessed the (a) left ventricular function by measuring the ejection fraction, (b) right ventricular function by measuring tricuspid annular plane systolic excursion, (c) the pulmonary artery systolic pressure in the presence of tricuspid regurge using the continuous-wave Doppler, and (d) the superior vena cava flow.
Statistical analysis of the data  were fed to the computer and analyzed using IBM SPSS software package, version 20.0. Qualitative data were described using the number and percent. Quantitative data were described using range (minimum and maximum), mean, SD, and median. The significance of the obtained results was judged at the 5% level. Comparison between different groups regarding categorical variables was tested using the χ2 test. When more than 20% of the cells have expected count less than 5, correction for χ2 was conducted using Fisher’s exact test or Monte Carlo correction. If it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, nonparametric tests were used. For normally distributed data, the comparison between two independent populations was done using independent Student t test. For abnormally distributed data, the comparison between two independent populations was done using Mann–Whitney test.
Approval for the study was obtained from the Department and Faculty Ethical Review Committee. Moreover, informed consent was obtained from all parents.
| Results|| |
During the whole period of the study, 2882 full-term babies were born, and those born in the period from March till May 2018 (group I-UCM) were 1512 babies. A total of 322 were eligible to be included, and 27 the babies were excluded (21 accidental hemorrhage, one chromosomal anomaly, three monozygotic twins, two brain malformations), 34 were referred to other facility, and 271 were discharged with no admission, leaving 30 admitted newborns.
Regarding the second group ICC (group of ICC) born during the period of June till August 41 babies were excluded (36 accidental hemorrhage, two congenital heart disease, two brain anomalies, and one monozygotic twins), 30 other babies were referred to other facility, and 195 were discharged home, leaving us with 36 NICU admissions among this group.
The comparison between both the two studied groups regarding the demographic data yielded no statistical significance. However, birth weight was found to be significantly higher among the group I [intact umbilical cord milking (I-UCM group] ([Table 1]), and when correlating birth weight and time to breathe ([Figure 1]), no significant correlation was obtained.
|Figure 1 The correlation between birth weight and time to breathe among the studied neonates.|
Click here to view
There was a statistically significant difference between the two studied groups regarding time taken to clamp the cord ([Figure 2]). Statistically significant differences were encountered regarding the time to take the first breath ([Figure 3]), heart rate at 1 min, and saturation at 1 min in favor of group I (I-UCM group) ([Table 2]).
|Table 2 Comparison between the two studied groups according to the time of cord clamping and the newborn condition in the immediate 10 min postnatal|
Click here to view
The laboratory parameters (hemoglobin level and the hematocrit were significantly higher among the group I (I-UCM group); thus, the need for packed red blood cell transfusion was statistically lower among this group (0% among the group I vs. 19.4% among group II) (P=0.013). On the contrary, no statistically significant difference was encountered regarding either the total serum bilirubin level in the first 24 h or the need for phototherapy during the hospital stay ([Table 3]).
|Table 3 Comparison between the two studied groups according to different laboratory investigations|
Click here to view
There was no statistically significant difference between the two studied groups regarding the incidence of hypoxic–ischemic encephalopathy and its staging using Modified Sarnat and Sarnat staging, as shown in [Table 4].
|Table 4 Comparison between the two studied groups according to the presence of hypoxia among cases in each group and its stages according to the modified Sarnat and Sarnat staging|
Click here to view
No statistically significant differences were encountered between the two groups regarding the need for ventilation support on NICU admission, its type (invasive or noninvasive), or the duration of ventilation. The FiO2 was statistically lower in the milking group (group I), and the O2 saturation was statistically higher, although the O2 saturation was in the normally accepted range in the two groups. No statistically significant differences were encountered between hypoxiated cases in the two groups regarding their need for inotropic support or vasopressors ([Table 5]).
|Table 5 Comparison between hypoxiated cases in the two groups according to the need for cardiorespiratory support|
Click here to view
Of noteworthy, the mean arterial blood, the tricuspid annular plane systolic, and the ejection fraction (%) were statistically higher in the hypoxiated cases in the milking group in day 1 and day 2 ([Table 6]).
|Table 6 Comparison between hypoxiated cases in the two groups according to the mean arterial blood pressure, ejection fraction, and the tricuspid annular plane systolic excursion in the first 2 days of life|
Click here to view
The tricuspid regurgitation was statistically higher in the control group (group II). Thus, the incidence rate of pulmonary arterial hypertension among hypoxiated cases group II was statistically higher in day 2. Among them, 50% had moderate pulmonary hypertension, whereas most of those who had pulmonary hypertension in day 2 in the cord milking group were of mild degree ([Table 7]).
|Table 7 Comparison between hypoxiated cases in the two groups according to the tricuspid regurgitation and the incidence rate of pulmonary arterial hypertension and its stages|
Click here to view
| Discussion|| |
The focus of successful neonatal transition had been always the ventilatory changes and switch to pulmonary ventilation; the need of adequate perfusion and adequate hemodynamic transition came second on the attention of caring physicians. The amount of blood volume retained in the placenta if ICC is applied would raise the question of immediate neonatal volume depletion and subsequent altered and affected neonatal transition. Such hypothesis raised the idea that placental transfusion would help transition especially in some asphyxiated babies and delayed clamping if done via I-UCM would not affect the resuscitation efforts .
The time of cord clamping reordered in our study among the milking group was statistically higher (13.07±2.68 s in the milking group vs. 7.94±2.28 s in the control group, P<0.001) ([Table 2]). It was reported by Katheria et al.  that UCM takes nearly the same time as ICC (14 s for UCM vs. 11 s in ICC group). The time to clamp the cord was not significantly different between the groups in their study, and interestingly, they noted that ICC did not occur within seconds of birth. Actually, Katheria et al.  mentioned that UCM takes no longer than 20 s, the same was found in our study, but it was statistically higher than the time taken in ICC group. The shorter time taken to clamp the cord in the ICC (control) group in our study may be owing to the rush of the obstetrician to clamp the cord and give that depressed term newborn to the neonatal resident to resuscitate.
Apgar scores at 1, 5, and 10 min were statistically higher in favor of I-UCM group [5 (2–7), 8 (4–9), and 10 (9–10) in comparison with 4 (2–6), 7 (4–9), and 9 (7–10) in ICC group] ([Table 2]). Girish et al.  reported, in a study that was conducted to evaluate the feasibility and safety of UCM in term neonates who were depressed at birth, that Apgar score at 1 min was higher in UCM at 6 (0–8) versus 5 (0–7) in the no-UCM group, but was not statistically significant and nearly equal scores between the two groups at 5 and 10 min. Kaempf et al.  reported that delayed cord clamping in premature newborns less than 1500 g had statistically higher Apgar score at 1 min [7 (1–9)] in the delayed versus [5 (0–10)] in the immediate clamping group. This could be explained as placental transfusion augments the circulation volume, and this is a vital physiological factor that can improve organ perfusion and may facilitate the neonatal transition.
UCM does not aggravate the depressed newborns’ condition nor resulted in an aggressive resuscitation effort, as no statistically significant differences were encountered regarding resuscitation requirements in the two studied groups ([Table 2]). Those who required initial steps among the milking group were 46.7 versus 36.1% among ICC group. Those who required more advanced resuscitation effort (positive airway pressure, endotracheal tube (ETT) or ETT and chest compression) among the milking group were 53.3 versus 63.9% in the ICC group, with P value of 0.851. Similar findings were reported by Girish et al.  (16% required ETT in the UCM group vs. 10% in the no-UCM group; P=0.8). Moreover, Katheria et al.  conducted a retrospective study on the effect of milking on term newborns with acidosis and found that those who required resuscitation (i.e. required continuous positive airway pressure or mechanical ventilation in the first 10 min after delivery) among the UCM group were 38 versus 56% among those who received ICC, with P value of 0.07.
Multiple linear regression for factors predicting the time to breathe among the studied neonates found that among the independent variables (birth weight and cord clamping time), the cord clamping time was the statistically significant variable. This indicates that milking the cord facilitated early breathing among the milking group. In the current study, the time of the first breath or cry was statistically shorter in the milking group at 54±50.11 vs. 141.9±165.7 s in the control (ICC) group, as illustrated in [Table 2], which was approved and explained by the study performed by Katheria et al.  reporting that continued placental transfusion for a long time led to the establishment of respiration faster and earlier first breath/cry. In the current study, regarding the incidence of hypoxic–ischemic encephalopathy, no statistically significant differences were encountered between the two groups (70% in milking group vs. 88.9% in the control group) ([Table 4]). Girish et al.  reported in a similar study that 50% in the UCM group vs 51% in the control group were diagnosed to have HIE.
The need of ventilatory support and duration of ventilation is a parameter to assess the recovery of both groups after delivery, where both groups had no statistical difference in that parameter ([Table 5]). Such findings were noticed also by Girish et al.  and Katheria et al. . Interestingly, we have found a statistically significant difference between hypoxiated cases in the two groups regarding the inspired oxygen fraction (FiO2) in day 1 and regarding the O2 saturation in the first 2 days of life (a higher FiO2 requirement among hypoxiated cases in the control group), whereas a higher O2 saturation was found among hypoxiated cases in the milking group in day 1 and day 2, respectively. Yet, O2 saturation was within normally accepted range among hypoxiated in both groups. We could not attribute the lower FiO2 required among the milking group to the effect of milking in reducing the pulmonary vascular resistance. As the distribution of cases regarding their lung pathologies was not studied, further studies are required to evaluate the effect of milking on the FiO2 requirement in relation to different lung pathologies.
Regarding hemodynamic assessment, the mean blood pressures measured at 6–12 h and at 24–36 h after birth were higher in the milking group than the control group, but the values were still within the normal range. The values of the mean arterial blood pressure among the control group were lower than the reference values reported by Nuntnarumit et al.  according to the gestational age and the postnatal age in hours. This may be caused by the effect of ICC on those depressed term newborn. Regarding the EF%, in hypoxiated cases, EF% was statistically higher in the milking group (group I) than the control group (group II) (71.4±6.28 and 72.07±7.34% in group I vs. 66.88±7.97 and 66.31±9.09% in group II at 12 and at 36 h of life, respectively). This could be justified by the effect of I-UCM on the cardiovascular transition of depressed newborn. Zaramella et al.  conducted a study to assess the effect of early versus late cord clamping on the cardiac function in healthy term newborns and reported that EF% between the two groups showed no significant differences [72% (57–93%) in late-clamping group vs. 72% (43–88%) in the early clamping group]. Such results could highlight the effect of placental transfusion in depressed babies that might need such transfusion to normalize their EF%.
On the contrary, those subjected to ICC and perinatal asphyxia had subnormal tricuspid annular plane systolic excursion values. This could be explained by the role of UCM in early relaxation of the PVR and thus decreasing the afterload faced by the right ventricle, hence a higher value but still in the normal range for those who underwent I-UCM. Lastly, tricuspid regurgitation was statistically higher among hypoxiated cases in the control group at 36 h of life. So, the hypoxiated cases in the control group had a statistically higher incidence of pulmonary arterial hypertension (62.5%) than the hypoxiated cases in the milking group (33.3%). This difference could not be attributed to the effect of therapeutic hypothermia, as the cases in both groups were subjected to the same therapy but could be attributed to the better transitioning and adaptive effect in those who received I-UCM.
| Conclusions|| |
Placental transfusion in the form of I-UCM is feasible to perform and does not hinder resuscitation efforts, with no effect on Apgar score. Babies who were subjected to such intervention had better hemodynamic assessment by functional echocardiography, a real time tool for neonatal hemodynamic assessment.
The research was supported by Alexandria Faculty of Medicine.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wall SN, Lee ACC, Niermeyer S, English M, Keenan WJ, Carlo W et al.
Neonatal resuscitation in low‐resource settings: what, who, and how to overcome challenges to scale up?. Int J Gynecol Obstetr 2009; 107(Supplement):47–64.
Katheria AC, Brown MK, Rich W, Arnell K. Providing a placental transfusion in newborns who need resuscitation. Front Pediatr 2017;5:1.
Sutton MSJ, Theard MA, Bhatia SJS, Plappert T, Saltzman DH, Doubilet P. Changes in placental blood flow in the normal human fetus with gestational age. Pediatr Res 1990;28:383–387.
Hooper SB, Te Pas AB, Lang J, van Vonderen JJ, Roehr CC, Kluckow M et al.
Cardiovascular transition at birth: a physiological sequence. Pediatr Res 2015; 77:608–614.
Bhatt S, Alison BJ, Wallace EM, Crossley KJ, Gill AW, Kluckow M et al.
Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol 2013; 591:2113–2126.
Farrar D, Airey R, Law GR, Tuffnell D, Cattle B, Duley L. Measuring placental transfusion for term births: weighing babies with cord intact. BJOG 2011;118:70–75.
Committee on Obstetric P. Committee opinion No. 684: delayed umbilical cord clamping after birth. Obstet Gynecol 2017; 129:e5.
Katheria AC, Truong G, Cousins L, Oshiro B, Finer NN. Umbilical cord milking versus delayed cord clamping in preterm infants. Pediatrics 2015;136:61–69.
Giesinger RE, Bailey LJ, Deshpande P, McNamara PJ. Hypoxic-ischemic encephalopathy and therapeutic hypothermia: the hemodynamic perspective. J Pediatr 2017;180:22–30.
Mertens L, Seri I, Marek J, Arlettaz R, Barker P, McNamara P et al.
Targeted neonatal echocardiography in the neonatal intensive care unit: practice guidelines and recommendations for training: writing group of the American Society of Echocardiography (ASE) in collaboration with the European Association of Echocardiography (EAE) and the Association for European Pediatric Cardiologists (AEPC). Eur J Echocardiogr 2011; 12:715–736.
Mercer JS, Erickson‐Owens DA. Is it time to rethink cord management when resuscitation is needed? J Midwifery Women’s Health 2014; 59:635–644.
Rabe H, Jewison A, Alvarez RF, Crook D, Stilton D, Bradley R et al.
Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial. Obstetr Gynecol 2011; 117:205–211.
Kirkpatrick L, Feeney B. A simple guide to IBM SPSS: for version 20.0: Nelson education. Belmont, Calif.: Wadsworth, Cengage Learning; 2013.
Katheria A, Blank D, Rich W, Finer N. Umbilical cord milking improves transition in premature infants at birth. PLoS ONE 2014; 9:e94085.
Girish M, Jain V, Dhokane R, Gondhali SB, Vaidya A, Aghai ZH. Umbilical cord milking for neonates who are depressed at birth: a randomized trial of feasibility. J Perinatol 2018; 38:1190–1196.
Kaempf JW, Tomlinson MW, Kaempf AJ, Wu Y, Wang L, Tipping N et al.
Delayed umbilical cord clamping in premature neonates. Obstetr Gynecol 2012; 120(2 Part 1):325–330.
Katheria A, Mercer J, Brown M, Rich W, Baker K, Harbert MJ et al.
Umbilical cord milking at birth for term newborns with acidosis: neonatal outcomes. J Perinatol 2018; 38:240–244.
Katheria AC, Brown MK, Faksh A, Hassen KO, Rich W, Lazarus D et al.
Delayed cord clamping in newborns born at term at risk for resuscitation: a feasibility randomized clinical trial. J Pediatr 2017; 187:313–317.
Nuntnarumit P, Yang W, Bada-Ellzey HS. Blood pressure measurements in the newborn. Clin Perinatol 1999; 26:981–996.
Zaramella P, Freato F, Quaresima V, Secchieri S, Milan A, Grisafi D et al.
Early versus late cord clamping: effects on peripheral blood flow and cardiac function in term infants. Early Hum Dev 2008; 84:195–200.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]