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Effects of Delayed versus Early Cord Clamping on Healthy Term Infants
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to study maternal and infant effects of delayed cord clamping (≥180 seconds, DCC) compared to early (≤10 seconds, ECC) in a randomised controlled trial. Practice and guidelines regarding when to clamp the cord vary globally, and different meta-analyses have shown contradictory conclusions on benefits and disadvantages of DCC and ECC.

The study population consisted of 382 term infants born after normal pregnancies and randomised to DCC or ECC after birth. The primary objective was iron stores and iron deficiency at 4 months of age, but the thesis was designed to investigate a wide range of suggested effects associated with cord clamping.

Paper I showed that DCC was associated with improved iron stores at 4 months (45% higher ferritin) and that the incidence of iron deficiency was reduced from 5.7% to 0.6%. Neonatal anaemia at 2-3 days was less frequent in the DCC group, 1.2% vs. 6.3%. There were no differences between the groups in respiratory symptoms, polycythaemia, or hyperbilirubinaemia.

In paper II we demonstrated that DCC versus ECC was not associated with higher risk for maternal post partum haemorrhage and rendered a comparable ratio of valid umbilical artery blood gas samples.

In paper III, the Ages and Stages Questionnaire was used to assess neurodevelopment at 4 months. The total scores did not differ, but the DCC group had a higher score in the problem-solving domain and a lower score in the personal-social domain. Immunoglobulin G level was 0.7 g/L higher in the DCC group at 2–3 days, but did not differ at 4 months. Symptoms of infection up to 4 months were comparable between groups.

Finally, in paper IV, iron stores and neurodevelopment were similar between groups at 12 months. Gender specific outcome on neurodevelopment at 12 months was discovered, implying positive effects from DCC on boys and negative on girls.

We conclude that delaying umbilical cord clamping for 180 seconds is safe and associated with a significantly reduced risk for iron deficiency at 4 months, which may have neurodevelopmental effects at a later age.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 893
Keyword [en]
active management, birth, breast feeding, cord clamping, ferritin, growth, haemoglobin, human infant, infections, iron, iron deficiency, iron deficiency anemia, iron status, morbidity, neurodevelopment, randomised controlled trial, umbilical cord
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-198167ISBN: 978-91-554-8647-1 (print)OAI: oai:DiVA.org:uu-198167DiVA: diva2:615347
Public defence
2013-05-23, Rosénsalen, Ingång 95/96, Akademiska Barnsjukhuset, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2013-04-29 Created: 2013-04-10 Last updated: 2013-08-30Bibliographically approved
List of papers
1. Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial
Open this publication in new window or tab >>Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial
2011 (English)In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 343, d7157- p.Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

Design: Randomised controlled trial.

Setting: Swedish county hospital.

Participants: 400 full term infants born after a low risk pregnancy.

Intervention: Infants were randomised to delayed umbilical cord clamping (>= 180 seconds after delivery) or early clamping (<= 10 seconds after delivery).

Main outcome measures: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

Results: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 mu g/L v 81 mu g/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

Conclusions: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-168430 (URN)10.1136/bmj.d7157 (DOI)000299016400004 ()
Available from: 2012-02-10 Created: 2012-02-10 Last updated: 2017-12-07Bibliographically approved
2. Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial
Open this publication in new window or tab >>Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial
Show others...
2013 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, 567-574 p.Article in journal (Refereed) Published
Abstract [en]

Objective

To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling.

Design

Secondary analysis of a parallel-group, single-center, randomized controlled trial.

Setting

Swedish county hospital.

Population

382 term deliveries after a low-risk pregnancy.

Methods

Deliveries were randomized to DCC (≥180 seconds, n = 193) or ECC (≤10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO2.

Main outcome measures

PPH and proportion of valid blood gas samples.

Results

The differences between the DCC and ECC groups with regard to PPH (1.2%, p = 0.8) and severe PPH (-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between the DCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC.

Conclusions

Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective.

National Category
Medical and Health Sciences
Research subject
Medical Science; Obstetrics and Gynaecology; Pediatrics
Identifiers
urn:nbn:se:uu:diva-196866 (URN)10.1111/j.1600-0412.2012.01530.x (DOI)000319060200011 ()22913332 (PubMedID)
Available from: 2013-03-14 Created: 2013-03-14 Last updated: 2017-12-06Bibliographically approved
3. Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial
Open this publication in new window or tab >>Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial
2013 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 5, 525-531 p.Article in journal (Refereed) Published
Abstract [en]

AIM:

To investigate the effect that delayed and early umbilical cord clamping have on neurodevelopment, immunoglobulin G (IgG) and symptoms of infection during the first 4 months of life.

METHODS:

Full-term infants (n = 382) were randomised to delayed (≥180 sec) or early cord clamping (≤10 sec). The Ages and Stages Questionnaire (ASQ) was used to assess neurodevelopment at 4 months. Immunoglobulin G was measured at birth, 2-3 days and 4 months. Parents recorded any symptoms indicating infection during the first 4 months of life.

RESULTS:

The total scores from the ASQ did not differ between groups. However, the delayed cord clamping (DCC) group had a higher mean (SD) score in the problem-solving domain [55.3 (7.2) vs. 53.5 (8.2), p = 0.03] at 4 months and a lower mean (SD) score in the personal-social domain [49.5 (9.3) vs. 51.8 (8.1), p = 0.01]. The IgG level was higher in the DCC group at 2-3 days (11.7 vs. 11.0 g/L, p = 0.004), but did not differ between the groups at 4 months. Symptoms of infection were comparable between the groups.

CONCLUSION:

Delayed cord clamping did not affect overall neurodevelopment or symptoms of infection up to 4 months of age, but may have an impact on specific neurodevelopmental domains.

National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-196867 (URN)10.1111/apa.12168 (DOI)000317361400029 ()23336628 (PubMedID)
Available from: 2013-03-14 Created: 2013-03-14 Last updated: 2017-12-06Bibliographically approved
4. A randomized trial of delayed versus early cord clamping: iron status and neurodevelopment at 12 months of age
Open this publication in new window or tab >>A randomized trial of delayed versus early cord clamping: iron status and neurodevelopment at 12 months of age
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objectives: To investigate effects of delayed umbilical cord clamping, as compared to early, on iron status and infant development at 12 months of age.

Study design: Term infants (n = 382) were randomly assigned to delayed (≥180 sec) or early (≤10 sec) umbilical cord clamping. Follow up at 12 months of age included evaluation of iron status (ferritin, transferrin saturation, transferrin receptor, reticulocyte hemoglobin equivalent and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire.

Results: At 12 months 347 infants were assessed. The two randomization groups did not differ in iron status or in neurodevelopment; 13 had iron deficiency and only one infant had iron deficiency anemia. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ were infant sex and breastfeeding within one hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that delayed cord clamping was associated with a 5 points higher ASQ score among boys, but a 12 points lower score in girls, out of a maximum of 300 points.

Conclusions: Delayed cord clamping increases neonatal hemoglobin levels and improves iron status at four months of age, but does not affect ferritin levels or neurodevelopment assessed by ASQ in a selected population of healthy term born infants. However, minor effects on neurodevelopment may not be possible to demonstrate with the size of the study population and the chosen method for assessment. The current data indicate that effects of delayed cord clamping may differ according to infant sex and that boys may benefit more from delayed cord clamping than girls.

National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-198166 (URN)
Available from: 2013-04-10 Created: 2013-04-10 Last updated: 2013-08-30

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