Effect of Intact Umbilical Cord Milking on Neonatal and First Year Neurodevelopmental Outcomes in Very Preterm Infants.

Preterm Infant Clinical Trial

— Cord-milking  

Official title:

Effect of Intact Umbilical Cord Milking Versus Immediate Cord Clamping on Neonatal Outcomes and First Year Neurodevelopmental Outcomes in Very Preterm Infants - A Randomised Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03200301
• Other study ID #: Jubilee MMCRI
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 1, 2018
• Est. completion date: April 30, 2024

Study information

• Verified date: March 2024
• Source: Jubilee Mission Medical College and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesise that intact umbilical cord milking (I-UCM) will reduce neonatal morbidity and improve long term neurodevelopmental outcome in very preterm infants. All babies born less than 32 weeks gestation, meeting the inclusion criteria will be randomly assigned to either I-UCM or immediate cord clamping (ICC) and their short and long term outcome measures analyzed.

Description:

Optimizing placental transfusion at birth promotes a more physiologic transition from intrauterine to extrauterine life. There is increasing evidence about the benefits of enhanced placental transfusion in improving neonatal outcomes, such as higher hemoglobin concentration, improved hemodynamic stability, reduced incidence of intraventricular hemorrhage, less need for blood transfusions and better neurodevelopmental outcome in preterm infants. The investigators propose to evaluate the the safety and effectiveness of I-UCM versus ICC in mothers undergoing preterm delivery before 32 weeks, by randomly assigning them to one of two groups - study and control. The study group will undergo I-UCM during delivery and the control group will have ICC, which is the current standard of care. Both groups will subsequently receive routine care for mother and infant. In the study group the infants will be placed at or ∼20 cm below the level of the placenta and about 20 cm of the intact umbilical cord will be milked towards the umbilicus three times. The technique consists of pinching the cord close to the placenta and milking about 20 cm segment of the cord proximal to the umbilicus, towards the infant over a 2-second duration. The cord will then be released and allowed to refill with blood for a brief 2-second pause between each milking motion. After completion of milking three times, the cord will be clamped close to the umbilicus and the neonate handed over to the neonatal team. The procedure of cord milking will be completed within 20 seconds. Prenatal and delivery data will be collected from the mother's charts. Infant data will be collected from hospital admission records and from follow up for a period up to 12 months of corrected age. The infant data collected will include hemoglobin levels at birth, incidence and severity of intraventricular hemorrhage in the first week of life and neonatal morbidity (resuscitation measures, peak bilirubin, need for phototherapy and blood transfusion, sepsis, necrotizing enterocolitis, retinopathy of prematurity and chronic lung disease) and mortality. The neurodevelopmental status of both the study and control group of infants will be assessed at 6 months and one year of corrected age. The investigators hypothesize that I-UCM provides a greater placental transfusion and better neonatal outcomes when compared to ICC. It is a simple procedure which can be practiced universally and of great relevance to both developed and developing countries.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Minute to 5 Minutes

Eligibility

Inclusion Criteria:

• All the preterm infants of less than 32 weeks of gestation born of consenting parents in the hospital

Exclusion Criteria:

• Neonates depressed at birth, MCMA, MCDA Twin pregnancy (DCDA twins are included), Severe IUGR in antenatal scans (< 10th Centile), Known case of Hydrops fetalis, Known major congenital anomaly, Placenta previa and abruptions, bleeding, accreta, nuchal cord, anhydramnios, PROM > 2 weeks before 24 weeks and Refusal to Consent by the Parents

Related Conditions & MeSH terms

• Premature Birth
• Preterm Infant
• Umbilical Cord Milking

Intervention

Procedure:
• Intact Umbilical Cord Milking
Immediately after delivery, the infant will be placed at or ~20 cm below the level of the placenta and about 20 cm of the intact umbilical cord will be milked towards the umbilicus three times. The technique consists of pinching the cord close to the placenta and milking about 20 cm segment of the cord proximal to the umbilicus, towards the infant over a 2-second duration. The cord will then be released and allowed to refill with blood for a brief 2-second pause between each milking motion. After completion of milking three times, the cord will be clamped close to the umbilicus and the neonate handed over to the neonatal team. The procedure of cord milking will be completed within 20 seconds.

Locations

Country	Name	City	State
India	Jubilee Mission Medical College & Research Institute	Thrissur	Kerala

Sponsors (1)

Lead Sponsor	Collaborator
Jubilee Mission Medical College and Research Institute

Country where clinical trial is conducted

India, 

References & Publications (12)

Al-Wassia H, Shah PS. Efficacy and safety of umbilical cord milking at birth: a systematic review and meta-analysis. JAMA Pediatr. 2015 Jan;169(1):18-25. doi: 10.1001/jamapediatrics.2014.1906. — View Citation

Boere I, Roest AA, Wallace E, Ten Harkel AD, Haak MC, Morley CJ, Hooper SB, te Pas AB. Umbilical blood flow patterns directly after birth before delayed cord clamping. Arch Dis Child Fetal Neonatal Ed. 2015 Mar;100(2):F121-5. doi: 10.1136/archdischild-2014-307144. Epub 2014 Nov 11. — View Citation

Committee on Obstetric Practice, American College of Obstetricians and Gynecologists. Committee Opinion No.543: Timing of umbilical cord clamping after birth. Obstet Gynecol. 2012 Dec;120(6):1522-6. doi: 10.1097/01.AOG.0000423817.47165.48. — View Citation

Ghavam S, Batra D, Mercer J, Kugelman A, Hosono S, Oh W, Rabe H, Kirpalani H. Effects of placental transfusion in extremely low birthweight infants: meta-analysis of long- and short-term outcomes. Transfusion. 2014 Apr;54(4):1192-8. doi: 10.1111/trf.12469. — View Citation

Katheria AC, Brown MK, Rich W, Arnell K. Providing a Placental Transfusion in Newborns Who Need Resuscitation. Front Pediatr. 2017 Jan 25;5:1. doi: 10.3389/fped.2017.00001. eCollection 2017. — View Citation

Katheria AC, Truong G, Cousins L, Oshiro B, Finer NN. Umbilical Cord Milking Versus Delayed Cord Clamping in Preterm Infants. Pediatrics. 2015 Jul;136(1):61-9. doi: 10.1542/peds.2015-0368. — View Citation

Niermeyer S. A physiologic approach to cord clamping: Clinical issues. Matern Health Neonatol Perinatol. 2015 Sep 8;1:21. doi: 10.1186/s40748-015-0022-5. eCollection 2015. — View Citation

Nolan JP, Hazinski MF, Aickin R, Bhanji F, Billi JE, Callaway CW, Castren M, de Caen AR, Ferrer JM, Finn JC, Gent LM, Griffin RE, Iverson S, Lang E, Lim SH, Maconochie IK, Montgomery WH, Morley PT, Nadkarni VM, Neumar RW, Nikolaou NI, Perkins GD, Perlman JM, Singletary EM, Soar J, Travers AH, Welsford M, Wyllie J, Zideman DA. Part 1: Executive summary: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2015 Oct;95:e1-31. doi: 10.1016/j.resuscitation.2015.07.039. No abstract available. — View Citation

Rabe H, Diaz-Rossello JL, Duley L, Dowswell T. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev. 2012 Aug 15;(8):CD003248. doi: 10.1002/14651858.CD003248.pub3. — View Citation

Rabe H, Sawyer A, Amess P, Ayers S; Brighton Perinatal Study Group. Neurodevelopmental Outcomes at 2 and 3.5 Years for Very Preterm Babies Enrolled in a Randomized Trial of Milking the Umbilical Cord versus Delayed Cord Clamping. Neonatology. 2016;109(2):113-9. doi: 10.1159/000441891. Epub 2015 Dec 10. — View Citation

Safarulla A. A review of benefits of cord milking over delayed cord clamping in the preterm infant and future directions of research. J Matern Fetal Neonatal Med. 2017 Dec;30(24):2966-2973. doi: 10.1080/14767058.2016.1269319. Epub 2017 Jan 12. — View Citation

Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, Simon WM, Weiner GM, Zaichkin JG. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S543-60. doi: 10.1161/CIR.0000000000000267. No abstract available. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Haemoglobin levels at birth	Haemoglobin levels at birth	1 hour
Primary	Intraventricular Haemorrhage	Incidence and severity of Intraventricular Haemorrhage in the first week of life - Cranial Ultrasound done on day 7	7 days of life
Secondary	The resuscitation interventions required with and without umbilical cord milking.	The resuscitation interventions required that will be assessed are requirement of Continuous Positive Airway Pressure (CPAP), oxygen, mask and bag ventilation, endotracheal intubation and ventilation, chest compressions, drugs, and fluid boluses	20 minutes after delivery
Secondary	Resuscitation outcomes with and without umbilical cord milking.	Short term outcomes of resuscitation will be assessed using the validated Combined Apgar score (consisting of the Expanded and Specified Apgar scoring systems) introduced by Rudiger et al, in depressed neonates with and without UCM.; Ref:Dalili H, Nili F, Sheikh M, Hardani AK, Shariat M, Nayeri F (2015) Comparison of the Four Proposed Apgar Scoring Systems in the Assessment of Birth Asphyxia and Adverse Early Neurologic Outcomes. PLoS ONE 10(3): e0122116	20 minutes after delivery
Secondary	Incidence of hypotension	Incidence of hypotension	24 hours of life
Secondary	Requirement of inotropic support	Number of inotropes required for support	24 hours of life
Secondary	symptomatic polycythemia	The number of neonates with symptomatic polycythemia (defined as lethargy, plethora, jitteriness, tachycardia, tachypnea and with venous hematocrit > 65%).	48 hours of life
Secondary	Sepsis (culture positive)	Incidence of Sepsis (culture positive)	72 hours of life
Secondary	Peak bilirubin levels	Serum peak bilirubin levels	72 hours of life
Secondary	Requirement of phototherapy or exchange transfusion	Neonates requiring phototherapy or exchange transfusion will be evaluated according to the NICE guidelines and serum bilirubin levels will be interpreted according to the baby's age in hours. Physicians who assess the neonate and advice phototherapy or exchange transfusion will be blinded to the intervention.	72 hours of life
Secondary	Incidence of Necrotising Enterocolitis (NEC)	Incidence of Necrotising Enterocolitis as defined by modified Bell's Criteria	14 days of life
Secondary	Requirement of Oxygen	Requirement of Oxygen at 28 days of life and at 36 weeks gestation	36 weeks of gestational age
Secondary	Requirement of red blood cell transfusions	Requirement of red blood cell transfusions before discharge	4 weeks of life
Secondary	Number of days of Hospital Stay after Birth	Number of days of Hospital Stay after Birth	4 weeks of life
Secondary	Death prior to discharge	Death prior to discharge	4 weeks of life
Secondary	Serum iron stores	Serum iron stores (ferritin levels) at 6 weeks and 6 months of age	6 months of age
Secondary	Developmental Assessment Scales for Indian Infants (DASII)	Developmental Assessment Scales for Indian Infants (DASII) tests carried out at 6 months and 1 year of corrected age. The DASII scale is divided into motor scale and mental scale. The motor scale consists of 67 items and mental scale consists of 163 items. (P Phatak, et al, 1996)	1 year of corrected age