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

Study Overview
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Brief Summary
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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.

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

Conditions
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Iron Deficiency, Neonatal Hyperbilirubinemia

Intervention / Treatment
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* Procedure: Timing of clamping the umbilical cord


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 37 Weeks
Maximum Age: 42 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Early cord clamping (ECC)<br>Early cord clamping consisted of early (< 10 s) clamping of the umbilical cord and obtaining blood gas samples after clamping. | Procedure: Timing of clamping the umbilical cord<br>* The time passed after delivery until that the midwife stops circulation in the umbilical cord with a clamp.<br>* Other names: Delayed cord clamping is also called Late cord claming;|
| Other: Delayed cord clamping (DCC)<br>Delayed cord clamping consisted of delayed (> 180 s) clamping of the umbilical cord and obtaining blood gas samples before clamping (within 30 seconds). | Procedure: Timing of clamping the umbilical cord<br>* The time passed after delivery until that the midwife stops circulation in the umbilical cord with a clamp.<br>* Other names: Delayed cord clamping is also called Late cord claming;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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) | 
| 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) | 
| 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) | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Umbilical cord, cord clamping, iron, Ferritin, newborn, jaundice, infant, development, infections