Early Versus Delayed Cord Clamping at Term: Outcomes in Swedish Infants

Iron Deficiency Clinical Trial

Official title:

Early Versus Delayed Cord Clamping at Term: Outcomes in Swedish Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01245296
• Other study ID #: NATIBAR08
• Status: Completed
• Phase: N/A
• First received: October 13, 2010
• Last updated: August 19, 2014
• Start date: April 2008
• Est. completion date: May 2010

Study information

• Verified date: August 2014
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

Delayed clamping of the umbilical cord might prevent or slow the onset of iron deficiency by increasing the infant's iron endowment at birth. Compared with early clamping, a delay of around 2-3 min provides an additional 25-40 mL of blood per kg of bodyweight.

The results of previous intervention studies on delayed clamping are mixed, and few followed up infants beyond the perinatal period. All longer follow up studies have been performed in low income countries. The main objectives, therefore, was to assess whether delayed cord clamping improves hematological and iron status at 4 respective 12 months of age in a large sample of full-term, Swedish infants.

The investigators also choose to investigate if the timing of clamping the umbilical cord could affect rate of infections during the first four months of life and to assess the infants development at 4 and 12 months of age.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 392
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 37 Weeks to 42 Weeks

Eligibility

Inclusion Criteria:

• non-smoking mother

• healthy mother (no hemolytic disease, no treatment with any of the following drugs:

anticonvulsants, antidepressants, thyroid hormone, insulin, chemotherapy or cortisone),

• normal pregnancy (no preeclampsia, no diabetes, no prolonged rupture of membranes or signs of infection)

• single birth, term pregnancy (gestational age 37 +0 until 41 +6 weeks + days)

• expected vaginal delivery with cephalic presentation

• mother should be able to master Swedish well enough to participate in the study

• mother should live close enough to the hospital to be ready to return for follow up after four months.

Exclusion Criteria:

• Serious congenital malformation, syndrome or other congenital disease that can affect the outcome measures

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Hyperbilirubinemia
• Hyperbilirubinemia, Neonatal
• Iron Deficiency
• Neonatal Hyperbilirubinemia

Intervention

Procedure:
• Timing of clamping the umbilical cord
The time passed after delivery until that the midwife stops circulation in the umbilical cord with a clamp.

Locations

Country	Name	City	State
Sweden	Länsjukhuset i Halmstad	Halmstad	Halland

Sponsors (4)

Lead Sponsor	Collaborator
Uppsala University	County Council of Halland, Sweden, Halmstad County Hospital, Umeå University

Country where clinical trial is conducted

Sweden, 

References & Publications (13)

Andersson O, Domellöf M, Andersson D, Hellström-Westas L. Effect of delayed vs early umbilical cord clamping on iron status and neurodevelopment at age 12 months: a randomized clinical trial. JAMA Pediatr. 2014 Jun;168(6):547-54. doi: 10.1001/jamapediatri — View Citation

Andersson O, Domellöf M, Andersson D, Hellström-Westas L. Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial. Acta Paediatr. 2013 May;102(5):525-31. doi: 10.1111/apa.12168. Epub 2013 Feb 11. — View Citation

Andersson O, Hellström-Westas L, Andersson D, Clausen J, Domellöf M. Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial. Acta Obstet Gynecol Scand. 2013 May;92(5 — View Citation

Andersson O, Hellström-Westas L, Andersson D, Domellöf M. Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial. BMJ. 2011 Nov 15;343:d7157. doi: 10.1136/bmj.d7157. — View Citation

Begley CM, Gyte GM, Murphy DJ, Devane D, McDonald SJ, McGuire W. Active versus expectant management for women in the third stage of labour. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007412. doi: 10.1002/14651858.CD007412.pub2. Review. Update in: Cochrane Database Syst Rev. 2011;(11):CD007412. — View Citation

Ceriani Cernadas JM, Carroli G, Pellegrini L, Otaño L, Ferreira M, Ricci C, Casas O, Giordano D, Lardizábal J. The effect of timing of cord clamping on neonatal venous hematocrit values and clinical outcome at term: a randomized, controlled trial. Pediatrics. 2006 Apr;117(4):e779-86. Epub 2006 Mar 27. — View Citation

Chaparro CM, Fornes R, Neufeld LM, Tena Alavez G, Eguía-Líz Cedillo R, Dewey KG. Early umbilical cord clamping contributes to elevated blood lead levels among infants with higher lead exposure. J Pediatr. 2007 Nov;151(5):506-12. Epub 2007 Sep 17. — View Citation

Grajeda R, Pérez-Escamilla R, Dewey KG. Delayed clamping of the umbilical cord improves hematologic status of Guatemalan infants at 2 mo of age. Am J Clin Nutr. 1997 Feb;65(2):425-31. — View Citation

Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in full-term neonates: systematic review and meta-analysis of controlled trials. JAMA. 2007 Mar 21;297(11):1241-52. Review. — View Citation

McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD004074. doi: 10.1002/14651858.CD004074.pub2. Review. Update in: Cochrane Database Syst Rev. 2013;7:CD004074. — View Citation

Mercer JS. Current best evidence: a review of the literature on umbilical cord clamping. J Midwifery Womens Health. 2001 Nov-Dec;46(6):402-14. Review. — View Citation

van Rheenen P, de Moor L, Eschbach S, de Grooth H, Brabin B. Delayed cord clamping and haemoglobin levels in infancy: a randomised controlled trial in term babies. Trop Med Int Health. 2007 May;12(5):603-16. — View Citation

van Rheenen PF, Gruschke S, Brabin BJ. Delayed umbilical cord clamping for reducing anaemia in low birthweight infants: implications for developing countries. Ann Trop Paediatr. 2006 Sep;26(3):157-67. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Do time for clamping the umbilical cord affect children's hemoglobin and iron status at 4 months of age?	Using mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), reticulocyte hemoglobin, serum ferritin, transferrin saturation and soluble transferrin receptors to assess iron status	4 months of age (plus or minus three weeks)	Yes
Secondary	Do the time for clamping the umbilical cord affect children's hemoglobin and iron status at 12 months of age?	Using mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), reticulocyte hemoglobin, serum ferritin, transferrin saturation and soluble transferrin receptors to assess iron status.	12 months of age (plus or minus one month)	No
Secondary	Are the rates of successful umbilical arterial samples equal between the groups?	Arterial blood samples are obtained with different methods between groups: in the early clamped group samples are taken from the placental part of the clamped cord, in the delayed clamped group samples are taken before clamping in the still pulsating cord. At the same time umbilical venous samples are obtained. A arterial blood sample is assessed as successful when ph < 0.2 and partial pressure of carbon dioxide (pCO2) > 0.5 kPa compared to the venous sample.	Immediately after birth (within 30 seconds)	No
Secondary	Is there a difference in development as assessed by the Ages and Stages Questionnaire at 4 months of age?	Ages and Stages Questionnaire is a parent report questionnaire available for developmental screening of children from one month to 5 ½ years. 30 questions are divided into 5 developmental domains (communication, gross motor, fine motor, problem solving and personal-social). Total score and scores within separate domains from the 4-month questionnaire will be assessed.	4 months of age (plus or minus three weeks)	No
Secondary	Do the time for umbilical cord clamping affect incidence of infections during the first four months of life?	After birth of their child, until four months of age parents fill out a form where they daily note if their infant has intestinal or respiratory symptoms, as well as if the infant has middle ear infection, has visited a doctor, has had an antibiotic prescription or has been admitted into a hospital.	4 months of age (plus or minus three weeks)	No
Secondary	Is Reticulocyte hemoglobin a useful measure of iron stores at 2-3 days of age?	Reticulocyte hemoglobin (RetHE) is a novel measure suggested to describe iron status. Ret HE will be compared to other indicators of iron stores: mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), serum ferritin, transferrin saturation and soluble transferrin receptors	Mean 2 to 3 days of age (within 48-96 hours after birth)	No
Secondary	Do the time for umbilical cord clamping affect neonatal outcomes: anemia, polycythemia and need for phototherapy?	Anemia defined as hemoglobin < 145 g/L, polycythemia defined as hematocrit > 0.65.	Within 7 days after birth	Yes
Secondary	Is there any difference in post partum haemorrhage when using early cord clamping compared to delayed cord clamping with oxytocin administered after clamping?	Measuring time to placental abortion, post partal hemorrhage and mothers post partum need for blood transfusion	After giving birth until discharge from maternity ward	Yes
Secondary	Is there a difference in development as assessed by the Ages and Stages Questionnaire at 12 months of age?	Ages and Stages Questionnaire is a parent report questionnaire available for developmental screening of children from one month to 5 ½ years. 30 questions are divided into 5 developmental domains (communication, gross motor, fine motor, problem solving and personal-social). Total score and scores within separate domains from the 12-month questionnaire will be assessed.	12 months of age (plus or minus one month)	No
Secondary	Do the time for umbilical cord clamping affect Immunoglobulin G levels at 2-3 days of age?	Blood samples for metabolic screening are routinely taken as soon as possible after 2 days (48 hours) of age. At the same time samples for Immunoglobulin G is obtained.	Mean 2 to 3 days of age (within 48-96 hours after birth)	No
Secondary	Is Reticulocyte hemoglobin a useful measure of iron stores at 12 months of age?	Reticulocyte hemoglobin (RetHE) is a novel measure suggested to describe iron status. Ret HE will be compared to other indicators of iron stores: mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), serum ferritin, transferrin saturation and soluble transferrin receptors	12 months of age (plus or minus one month)	No
Secondary	Does the time for umbilical cord clamping affect the infants respiration within the first 6 hours of life?	Midwives observes the newborn infant at 1 hour and 6 hours of age and note presence of tachypnea (> 60 breaths/minute), grunting, nostril flaring and or retractions between or under the ribs.	Within 6 hours after birth	Yes