Early Versus Delayed Cord Clamping at Term: Neurodevelopmental Outcomes in Swedish Infants at 4 Years of Age
Condition: Developmental Delay; Iron Deficiency
MeSH terms: Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Observational

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 to early clamping, a delay in
      clamping in clamping of around 2-3 min provides an additional 25-40 mL of blood per kg of
      bodyweight to the newborn infant.

      The results of previous intervention studies on delayed clamping are mixed, and few have
      followed the infants beyond the perinatal period. All longer follow up studies have been
      performed in low income countries except for the investigators earlier study, showing less
      iron deficiency and improved iron stores after delayed cord clamping at 4 months of age.

      The main objective of the current study is to assess whether the time of cord clamping
      affects neurodevelopment at 4 years of age in a large sample of full-term, Swedish infants.
      The investigators hypothesis is that as delayed cord clamping improves iron stores at 4
      months, this could affect the child's development positively.
    

Detailed description: 
      Project description

      Iron deficiency is associated with neurodevelopmental delay and suboptimal cognitive
      function. Our hypothesis is that early cord clamping is associated with an increased risk for
      iron deficiency, and as a consequence increased risk for suboptimal infant development also
      in a country with high standard of living.

        -  Method

             1. Study cohort Four-hundred full-term infants, born to healthy mothers after normal
                pregnancies, were randomized to early or delayed cord clamping (at a hospital which
                practiced early cord clamping as standard practice). The infants were born during
                the time-period April 2008 to May 2009. Pregnant women were considered eligible if
                they met the following criteria: non-smoking, healthy mother (no haemolytic
                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. Furthermore,
                the mother should be able to master Swedish well enough to understand the meaning
                of the study. Mothers were given written and oral information about the trial at
                the maternal health care centre from 34 weeks of gestational age. Mothers
                fulfilling the inclusion criteria at the time of admission to the delivery ward
                were again given written and oral information about the study by the attending
                midwife and written informed consent was obtained. Randomization was performed in
                advance by computer in blocks of 20. When delivery was imminent, the midwife opened
                a sealed envelope containing the treatment allocation. The intervention in the
                early cord clamping (ECC) group consisted of double clamping of the umbilical cord
                within 10 seconds of the infant's delivery, and arterial and venous blood sampling
                from the clamped segment within 10 min. The intervention in the delayed cord
                clamping (DCC) group consisted of late (≥ 180 s) clamping of the umbilical cord and
                arterial and venous blood sampling from the unclamped cord within 30 seconds after
                birth, while the midwife was holding the child below the level of the uterus. In
                both randomization groups, all children were initially kept about 20 cm below the
                level of the mother's uterus for 30 seconds and then placed on their mother's
                chest. All other aspects of obstetric care during labour and delivery were managed
                according to the standard practice of care at the study hospital. Oxytocin was
                administered to all mothers immediately after cord clamping. The final
                participating mother-infant pairs available for statistical analysis were 189 in
                the ECC group and 193 in the DCC group.

             2. Follow up at 4 years of age

                Children will be asked to return for a follow up at 4 years of age for
                neuro-developmental testing including:

                  -  Cognitive testing with WPPSI (Wechsler Preschool and Primary Scale of
                     Intelligence)

                  -  Behavioral assessment with SDQ (Strengths and Difficulties Questionnaire), a
                     questionnaire for behavioural screening which is filled in by the parents

                  -  Assessment of psychomotor development with ASQ (Ages and Stages
                     Questionnaire), a questionnaire that is filled in by the parents

                  -  Selected items from Movement ABC (Assessment Battery for Children)

                Time plan The included children were born during the time period April 2008 to May
                2009, and they will become 4 years during 2012 and 2013. We aim to test them at the
                age of 4 years (April 2012 to May 2013). Additional research ethics permission for
                the follow up has been approved. Permission to translate and use the Ages and
                Stages Questionnaire (ASQ) for scientific purposes, has been sought from the
                publisher Brooks Publishing (as already approved for the previous versions at 4, 12
                and 36 months of age).

        -  Realization At approximately one month before the child's fourth birthday, the parents
           will receive a letter containing information about the study,including time and location
           for the testing, and the two questionnaires, SDQ and ASQ. The parents are asked to
           answer these questionnaires before the visit to the psychologist.

      The parents has also been informed about the planned neurodevelopmental testing and
      questionnaires at 4 years of age when they had another scheduled visit when the child was
      three years of age. The parents have the opportunity to contact the research assistant who
      can change the time for the visit. After the neurodevelopmental testing, the parents will
      receive a written report, and if abnormal results are discovered, due action will be taken.
    

Intervention name(s): Time to clamping of the umbilical cord after delivery
Intervention type(s): Procedure
Intervention description(s): The time after delivery of the newborn until the midwife stops the circulation in the umbilical cord with a clamp.
Other intervention name(s): Immediate cord clamping; Late cord clamping; Deferred cord clamping
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The eligble population consists of a group of 382 children who were included in a trial
        (NCT01245296) and randomized to either early or delayed cord clamping. The parents will be
        asked for consent for their child to participate in the current follow up study.
      
Keywords: Cord clamping; iron deficiency; Neurodevelopment