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Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes

  1. Susan J McDonald1,*,
  2. Philippa Middleton2,
  3. Therese Dowswell3,
  4. Peter S Morris4

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 11 JUL 2013

Assessed as up-to-date: 14 MAR 2013

DOI: 10.1002/14651858.CD004074.pub3


How to Cite

McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD004074. DOI: 10.1002/14651858.CD004074.pub3.

Author Information

  1. 1

    La Trobe University/Mercy Hospital for Women, Midwifery Professorial Unit, Melbourne, Victoria, Australia

  2. 2

    The University of Adelaide, ARCH: Australian Research Centre for Health of Women and Babies, The Robinson Institute, Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia

  3. 3

    The University of Liverpool, Cochrane Pregnancy and Childbirth Group, Department of Women's and Children's Health, Liverpool, UK

  4. 4

    Menzies School of Health Research, Division of Child Health, Darwin, Northern Territory, Australia

*Susan J McDonald, Midwifery Professorial Unit, La Trobe University/Mercy Hospital for Women, Level 4, Room 4.071, 163 Studley Road, Heidelberg, Melbourne, Victoria, 3084, Australia. s.mcdonald@latrobe.edu.au. sue.mcdonald@mercy.com.au.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 11 JUL 2013

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Characteristics of included studies [ordered by study ID]
Al-Tawil 2012

MethodsRandomised controlled trial, 2 arms with individual randomisation.


ParticipantsSetting: 180 women giving birth at a hospital in Saudi Arabia between 2010-11.

Inclusion criteria: Multigravid women who had received adequate antenatal care, with singleton, term pregnancy and without underlying medical disease of pregnancy complications and planning a normal vaginal delivery.

Exclusion criteria: Women who did not deliver vaginally, small for gestational age infants or with birthweight below 2500 g, neonates needing resuscitation or with respiratory difficulties, sepsis or congenital anomalies.


InterventionsEarly clamping: (90 women) immediate cord clamping (within 15 secs).

Delayed clamping: (90 women) delayed cord clamping (estimated from the time of shoulder delivery) with cord clamping after 3 minutes. The baby was put on the mother’s abdomen until the placenta was delivered. (If during the three minutes delay the infant showed any sign of compromise the cord was cut immediately to allow resuscitation.)

Administration of uterotonic not clear.


OutcomesBirthweight;

At 24 hours post birth and 3-5 months: infant haemoglobin, haematocrit, MCV, transferrin saturation, ferritin, and (at 24 hours post birth only) serum bilirubin. At 3-5 months MCV < 73 fL, serum transferrin < 20 µg/L, transferring saturation < 10% and anaemia (haemoglobin < 10.5 g/dL).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskIt was reported that the attending midwife opened a sealed envelope showing treatment allocation 20 minutes before the birth (it was not clear that all envelopes were accounted for and it appeared that there may have been post randomisation exclusions).

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding women and staff not feasible although it was stated that neonatal assessments and laboratory assessments were carried out by staff blind to randomisation group.

Incomplete outcome data (attrition bias)
All outcomes
High riskIt was stated that 180 women were randomised and that data at 3-5 months were available for 160. The analysis does not appear to have been on an ITT basis. It was stated that randomisation occurred 20 minutes before delivery, however it seems likely that there were post randomisation exclusions as several exclusion criteria would be  apparent at the birth (e.g. 18 infants requiring resuscitation were excluded).

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appeared comparable at baseline.

Andersson 2011

MethodsRandomised controlled trial: NCT01245296.


Participants400 women in Sweden. Normal birth at term.

Setting: Hospital in Halmstad, Sweden. Study conducted between April 2008 and September 2009.

Inclusion criteria:

Non-smoking, healthy women after normal pregnancy, singleton, term pregnancy, expected vaginal birth with cephalic presentation. Swedish speaking and living close enough to study hospital to attend for follow-up.

Exclusion criteria:serious congenital malformations, syndromes or other congenital diseases that could affect the outcome measures.


InterventionsEarly umbilical cord clamping (at or before 10 secs) versus delayed cord clamping (> 180 secs (3 minutes)).

In both groups the midwife was instructed to hold the baby 20 cm below the vulva for 30 secs and then place the baby on the mother’s abdomen. Oxytocin (10 IU) IV was administered immediately after clamping. The time to clamping was measured using a stopwatch.

Early clamping was the standard procedure before the study.


OutcomesPostpartum haemorrhage; length of third stage of labour; maternal blood transfusion; umbilical arterial and venous blood gases; jaundice; iron stores in infants at 2-3 days of age and 4 months post birth, polycythaemia; neurodevelopment at 4 months (assessed by ASQ), immunoglobulin G at birth, 2-3 days, and 4 months, symptoms of infection during first 4 months.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer randomisation in blocks (random number generator in MS Excel).

Allocation concealment (selection bias)Low risk “When delivery was imminent (expected within 10 minutes), the midwife opened a sealed, numbered, opaque envelope containing the treatment allocation)." 

Blinding (performance bias and detection bias)
All outcomes
Unclear riskMother and midwife were not blinded. Doctors carrying out neonatal examinations and laboratory staff performing analyses were blind to group allocation.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThere were a small number of post-randomisation exclusions (18/400) however, for many outcomes there were missing data. For primary outcomes (haemoglobin and iron status at 4 months 347/400 were followed up (87%); loss to follow-up was similar in the two arms of the trial; neurodevelopmental outcomes were measured in a subset of infants at 4 months (180 in the early clamping group and 185 in the late clamping group).

Selective reporting (reporting bias)Unclear riskUnable to assess (assessment from published study report only). 

Other biasUnclear riskGroup characteristics appeared similar at baseline. It was stated that routine care was early clamping.

Cernadas 2006

MethodsRandomised controlled trial.


ParticipantsWomen who had an uneventful cephalic vaginal or caesarean section birth, and singleton pregnancy at term; consented at 36 weeks' gestation visit.
276 women randomised.
2 obstetrical units in Argentina.

Exclusion criteria included diabetes, pre-eclampsia, hypertension, evidence of IUGR (estimated weight < 10th percentile), congenital malformation.


Interventions3 interventions were compared.
1. Early umbilical cord clamping (within 1st 15 secs of birth).
n = 93 [88/93 received the intervention - no cause given for 5 changes].
2. Cord clamping at 1 minute after birth
n = 91 [83/91 received the intervention - 8 changes (2 no breathing in the first 10 secs; 1 tight nuchal cord; 2 with both no breathing in first 10 secs and tight nuchal cord; 1 other cause; 2 no cause)].
3. Cord clamping at 3 minutes after birth.
n = 92 [83/92 received the intervention - 9 changes (4 no breathing in the first 10 secs; 1 no breathing in the first 10 secs and tight nuchal cord; 1 secondary apnoea; 1 spontaneous third stage; 1 amniotic fluid stained with meconium; 1 no cause)].

The latter 2 timing interventions were considered to be delayed.

In vaginal births, if the cord clamping allocation was delayed, the infant was placed in the mother's arm while awaiting cord clamping. If a caesarean birth, the infant was placed on the mother's lap and swaddled to prevent heat loss while awaiting cord clamping.

States no additional interventions were performed - interpret as no oxytocics?


OutcomesMaternal outcomes: postpartum blood loss volume and maternal haematocrit at 24 hours post birth.
Infant outcomes: newborn venous haematocrit at 6 hours after birth, neonatal haematocrit and plasma bilirubin levels at 24 and 48 hours of age, early neonatal mortality and morbidity (tachypnoea, respiratory grunting, respiratory distress, jaundice, seizures, sepsis, necrotising enterocolitis), admission to NICU, newborn length of hospital stay, any neonatal disease that occurred between birth and 1 month, weight and method of feeding at 1 month.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers - stratified by hospital and then by mode of birth within each hospital. Variable length blocks were used.

Allocation concealment (selection bias)Low riskAllocation by sealed opaque sequentially numbered envelopes - the allocation was read out to the attending clinician.Staff responsible for random generation and allocation concealment processes were not involved in the recruitment phase of the trial.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskPaediatricians assessing the outcomes were unaware of the assigned interventions.
Nature of the intervention meant that others could not be blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow-up: primary outcome was not measured in:
early 3/93; late 1 minute 1/91; late 3 minutes 0/92.

Selective reporting (reporting bias)Unclear riskAssessment from published study report only.

Other biasUnclear riskMore than a quarter of the women included had caesarean births. This may mean data from this study are affected by neonatal clinicians attending the delivery. In the past, babies delivered by caesarean were routinely admitted to special, or neonatal intensive care. In this study the number of caesarean births was balanced in the intervention and control groups so the impact of including data for these women is not clear.

Chaparro 2006

MethodsRandomised controlled trial.


Participants476 mother-infant pairs were randomised.
Women at term (equal to or greater than 36 weeks' and less than 42 weeks' gestation, where a vaginal birth of a healthy singleton infant was anticipated, the woman planned to breastfeed for at least 6 months, was a non-smoker, was able to return for follow-up visits and there were no complicating medical or obstetric factors.

Exclusion criteria applied after birth were low birthweight (< 2500 g) and major congenital malformations.

Setting: large obstetrics hospital in Mexico City, Mexico.


InterventionsEarly clamping (10 secs after birth) (n = 239);.
late clamping (2 minutes after birth) (n = 237).

Any condition arising that necessitated earlier clamping was adhered to.


OutcomesMaternal: estimated maternal blood loss at birth.
Infant: haematological and iron status at 6 months of age, newborn haematocrit and reported neonatal jaundice between birth and 14 days of age, exclusive breastfeeding.


NotesJaundice was self-report by mother, and so was not entered under the outcome of clinical jaundice.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlocks of 4 generated by random digital generator in Microsoft Excel.

Allocation concealment (selection bias)Low riskNumbered index cards with allocation were sealed in numbered opaque envelopes ordered sequentially.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo mention of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses to follow-up: early group: 68/239 lost to follow-up at 6 months (27 no longer interested, 7 moved away, 28 could not be located, 5 lack of time, 1 infant ill);
leaving 171 who completed the study at 6 months. There were also 2 protocol violations (cord clamping more than 30 secs after the delivery of the infant's shoulders), 1 nuchal cord, 1 reason not recorded.
157 had full blood sample analysis.
Late group: 50/237 lost to follow-up at 6 months (25 no longer interested, 4 moved away, 16 could not be located, 3 lack of time, 1 infant died, 1 participation in other study), leaving 187 who completed the study at 6 months. There were also 52 protocol violations (clamping at less than 100 secs after delivery of infant's shoulders), 30 concerns for infant's condition, 15 forceps used, 3 infants born in labour room bed, 4 misunderstanding of treatment group.
171 had full blood analysis.

Selective reporting (reporting bias)Unclear riskAssessment from published study report only.

Other biasLow riskOther risk of bias not apparent.

Emhamed 2004

MethodsRandomised controlled trial.


Participants112 (104) women in a large Libyan hospital who consented during first stage of labour.
Exclusion criteria: women with known medical or obstetric problems, less than 37 weeks' or greater than 42 weeks' gestation.
Post randomisation exclusions were an infant weighing less than 2500 g, instrumental births, respiratory distress, congenital abnormalities or the need for early cord clamping.


InterventionsEarly (immediate) cord clamping (10 secs following birth (n = 46);
late cord clamping (when cord pulsation ceased) (n = 58).

Oxytocin given when cord clamping had been performed.


OutcomesMaternal: pre and post birth haemoglobin and haematocrit.
Infant: haemoglobin and haematocrit (including cord blood), polycythaemia, hyperviscosity and jaundice.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Low riskConsecutive allocation of opaque envelopes.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot stated.

Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow-up: 1 mother/baby pair from each group (1/58 late; 1/46 early) left hospital before reassessment and so were not available for those outcomes measured 16-24 hours after birth.
4/50 pairs from the early group and 4/62 from the late group were excluded after randomisation because of intrapartum asphyxia.

Selective reporting (reporting bias)Unclear riskAssessment from published study report only.

Other biasLow riskOther risk of bias not apparent.

Geethanath 1997

MethodsRandomised controlled trial.


Participants107 women (anticipating a term vaginal birth and not experiencing any medical or obstetric complications including anaemia of < 10 g/dL).

New Delhi hospital, India.

Post randomisation exclusions were applied in the presence of birth asphyxia, major congenital malformations.


InterventionsEarly cord clamping: cord clamped as soon as the infant was born;
Late clamping: cord clamped after the placenta had descended into the vagina during which time the infant was held 10 cm below the vaginal introitus.


OutcomesMaternal: haemoglobin shortly after giving birth.
Infant: cord blood at birth and venous blood sample at 3 months for ferritin and haemoglobin estimation.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random number sequences.

Allocation concealment (selection bias)Low riskAllocation by opaque, sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskPost randomisation exclusions were reported (presence of birth asphyxia, major congenital malformations) but no losses to follow-up are reported.

Selective reporting (reporting bias)Unclear riskNot clear from paper.

Other biasLow riskNo other obvious bias.

Gupta 2002

MethodsRandomisd controlled trial.


Participants102 infant-mother pairs - hospital born neonates born vaginally to pregnant women with anaemia (haemoglobin < 100 g/L at term)

Exclusion criteria: medical or pregnancy related complications e.g. eclampsia, severe heart failure, severe antepartum haemorrhage or rH iso-immunisation.
Post randomisation exclusions: Infants who needed resuscitation at birth or who had major congenital malformations.

Teaching hospital, New Delhi.


InterventionsEarly cord clamping group (cord clamped immediately after the birth of the infant), n = 53.
Late cord clamping (cord clamped after the placenta had descended into the vagina), n = 49 - during this time the infant was warmly wrapped and held below the level of the mothers abdomen but within 10 cm of the vagina.

4 mL of maternal venous blood was taken at the time of the birth, 4 mL of cord blood at birth and 4 mL venous blood from the infant at 3 months of age.

Infants were not given any medicinal iron supplementation during the study period.


OutcomesMaternal: haemoglobin at birth.

Infant: haemoglobin at 3 months, weight gain, feeding patterns, respiratory infections and diarrhoea.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random number sequences.

Allocation concealment (selection bias)Low riskAllocation concealed by opaque sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot stated.

Incomplete outcome data (attrition bias)
All outcomes
High riskPost randomisation exclusions: Infants who needed resuscitation at birth or who had major congenital malformations.

Losses to follow-up: at 3 months, 58 (57%) of the original 102 mother-infant pairs were available, 29 pairs in each group.

Selective reporting (reporting bias)Unclear riskNo explanation is offered for high level of attrition at 3 months so reporting bias is difficult to assess.

Other biasLow riskNo other obvious bias.

Jahazi 2008

MethodsDescribed as double-blind randomised controlled trial. A total of 64 women were allocated to either the early or delayed umbilical cord clamping arms via toss of a coin.


ParticipantsWomen with uncomplicated pregnancies, between 38 and 42 weeks gestation and anticipating a normal vaginal birth were deemed eligible for participation


InterventionsImmediately prior to birth women were randomised to receive either early cord clamping (30 secs) n = 30 women or delayed cord clamping (3 minutes) n = 34 women. Timing was observed by a midwife using a stopwatch from the time of complete birth of the baby. The infant was held supine at the level of the introitus. In the delayed cord clamping group the infant was placed on a table at the level of the introitus and wiped dry with a warm sterile towel. 1 mL of cord blood was collected immediately following cord clamping and 1 mL antecubital blood was collected from the infant at 2 hours and 18 hours post birth.

All women in the study received IM oxytocin (10 IU) following cord ligation. All infants were breastfed


OutcomesMaternal: duration of the third stage of labour.

Infant outcomes reported were: gestational age, birthweight, Apgars at 1 and 5 minutes, placental residual blood volume (PRCV)and estimated neonatal blood volume at birth (ENBV), haematocrit values at birth, 2 and 18 hours post birth.

It is mentioned in the article that clinical manifestations of polycythaemia were observed for at the time points listed for blood collection and at 5 days post birth but outcomes of those observations are not reported.


NotesFurther information requested from authors regarding clarification of randomisation? (stated that the trial was double blinded) but description in the paper would indicate that this is inaccurate. Also, asked if the polycythaemia data were available in a table format to enable the figures and comparisons of the individual components to be more accurately reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskToss of coin to determine randomisation to one of two groups.

Allocation concealment (selection bias)Unclear riskFurther information requested from authors.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskThe authors have stated the study was double blinded but the description is not that of a blinded trial. Further information has been sought from the authors.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskMore information has been requested from the authors related to the data for polycythaemia.

Selective reporting (reporting bias)Unclear riskInfants with Apgars less than 7 at 1 or 5 minutes were excluded from analysis, Infants who were small (< 10th percentile) or large (> 90th percentile) for gestational age were excluded as were infants with a cord blood haematocrit of < 40 or > 65 and infants with congenital abnormalities.

Other biasUnclear riskNot able to assess from data provided.

McDonald 1996

MethodsRandomised controlled trial.


ParticipantsAll women attending the antenatal clinic at King Edward Memorial Hospital, Western Australia randomised when a vaginal birth was thought to be imminent.
Exclusions: maternal refusal to participate in the study; caesarean section; breech delivery; multiple pregnancy; fetal indication (e.g., known fetal anomaly); preterm birth (< 37 completed weeks' gestation).

1000 women were randomised to the trial; the data of 37 women were excluded due to insufficient information available to include in the analyses, leaving data for 963 women available for analysis.


Interventions4 arms: early cord clamping and early uterotonic administration (n = 236);
late cord clamping and early uterotonic administration (n = 244); early cord clamping and late uterotonic administration (n = 244); late cord clamping and late uterotonic administration (n = 239).

Definitions: early cord clamping involved clamping immediately following birth of the body of the baby; late cord clamping occurred when cord pulsation had ceased or at 5 minutes if cord pulsation had not already ceased. This time limit was imposed to reduce the risk of compromising infants who may have any undiagnosed underlying conditions such as a PDA; early uterotonic administration involved administration at the time of birth of the anterior shoulder of the baby; late uterotonic administration was after the birth of the baby (literally) and if the cord clamping allocation was early, then it was allocated to be after the cord was clamped (i.e. not within 30 secs).


OutcomesMaternal: PPH = or > 500 mL, = or > 1000 mL; mean blood loss; need for blood transfusion; need for manual removal of placenta; length of third stage (> 30 minutes and > 60 minutes); need for therapeutic uterotonics; evacuation of retained products; inversion of the uterus; length of hospital stay.
Neonatal: Apgar score < 6 at 5 minutes; admission to NICU; jaundice requiring phototherapy (> 1 day); need for serum bilirubin test; breastfeeding at discharge.


NotesSample size: the initial sample size calculation was based on an anticipation that the PPH rate from a uterotonic choice trial (McDonald 1996) would be around 10%. It was calculated that a sample size of 3000 women would be required to have an 80% chance of detecting a 50% reduction in PPH at the 5% level of statistical significance. However, review during the trial by a Data Monitoring Committee determined that the PPH rate was greater than the 10% rate predicted, the actual recorded PPH rate being around 16%; this reduced the required sample size to ˜1,100 women.

Blood loss assessment: "the major endpoint of the study was PPH ascertained by measurement of collected blood spillage where possible and all other blood loss estimated by visual estimation. The trial could not be 'blind' at this point; the clinician carrying out the intervention was also attempting to assess the blood loss. The authors attempted to obtain objective indices of blood loss in the form of 1. postpartum haemoglobin, 2. calculation of the difference between antepartum and postpartum haemoglobin. Although these measures may not be reliable measures of the amount of blood loss by an individual, they are objective, independent of observer bias and were carried out on women in the trial without knowledge of which intervention was used".

Jaundice assessment: Clinicians assessing jaundice are not likely to have been aware of the allocation to early and late clamping groups.

The study was written up as a PhD thesis, a copy of which is available from the Pregnancy and Childbirth Group office. It has never been submitted for journal publication.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskList of computer-generated random numbers.

Allocation concealment (selection bias)Low riskOpaque, sealed, sequentially numbered envelopes kept at a central location in the delivery ward.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskThe trial could not be 'blind' as the clinician carrying out the intervention was also attempting to assess the blood loss. The authors attempted to obtain objective indices of blood loss in the form of 1. postpartum haemoglobin, 2. calculation of the difference between antepartum and postpartum haemoglobin. Although these measures may not be reliable measures of the amount of blood loss by an individual, they are objective, independent of observer bias and were carried out on women in the trial without knowledge of which intervention was used".

Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow-up: all women allocated to receive a particular timing option were included in the intended group with the exception of 37 women for whom no trial number was recorded (14/250 in early cord clamping and early uterotonic group; 6/250 in late cord clamping and early uterotonic group; 6/250 in early cord clamping and late uterotonic; and 11/250 in late cord clamping and late uterotonic group).

Selective reporting (reporting bias)Low riskFurther information on outcomes was available from the author.

Other biasLow riskNot apparent.

Nelson 1980

MethodsRandomised controlled trial. Randomisation: "assigned randomly" - no further details provided.


ParticipantsWomen considered to be at low obstetrical risk, interested in the Leboyer approach to birth, and intending to attend psychoprophylactic prenatal classes.

Exclusion criteria: giving birth before 36 weeks, not available for 3 day and 8 month assessments.


InterventionsEarly ('conventional') birth with cord clamping within 1 minute of birth (n = 26); median time of 45 secs.
Late (Leboyer method with cord clamped when it stopped pulsating); n = 28; median time of 180 secs.


OutcomesMaternal: length of first, second and third stages of labour, mother's experience of labour and birth, maternal psychological adjustment at 6 weeks, maternal perception of infant behaviour at 3 days, 6 weeks and 8 months postpartum (Carey Scales of Infant Temperament), PPH (blood loss threshold not defined), extension of episiotomy, infected episiotomy, endometritis, urinary tract infection.
Infant: perinatal asphyxia, hypothermia (one or more axillary temp > 35 C), respiratory rate more than 60, polycythaemia (24-hour capillary haemoglobin more than 25 g per 100 mL [more than 15.51 mmol/L]), jaundice, hyperbilirubinaemia (serum bilirubin more than 12 mg per 100 mL [more than 205.2 umol/L]).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"assigned randomly" - no further details provided.

Allocation concealment (selection bias)Unclear riskNo details provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskWomen and care providers would be aware of allocation. 2nd observer blinded for Brazelton Neonatal Behavioural Assessment Scale, infant Bayley Scales of Infant Development assessed blind.

Incomplete outcome data (attrition bias)
All outcomes
Low riskLosses to follow-up: 1/55 (dropped out from conventional (early clamping) group.

Selective reporting (reporting bias)Unclear riskAssessment from published study report only.

Other biasLow riskNot apparent.

Oxford Midwives 1991

MethodsRandomised controlled trial.


Participants554 women.

Setting: large teaching hospital in Oxford, UK.


InterventionsEarly clamping (as soon as possible after the birth) or late clamping (3 minutes after the birth).


OutcomesMaternal: PPH, manual removal of placenta.
Neonatal: respiratory problems e.g. transient tachypnoea, grunting, rib recession, heart or cardiovascular problems, clinical jaundice (whether jaundice had been noted, the duration and level of jaundice as indicated by serum bilirubin if blood samples were taken, whether treated with phototherapy), birthweight, feeding method, duration of cord adherence.


NotesData from 100 women recruited to pilot the trial design was subsequently included in the total of 554 women. It is not clear whether the pilot data was unblinded and therefore may have biased the larger trial.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskGeneration by random-number tables (simple unblocked and unstratified).

Allocation concealment (selection bias)Low riskSealed opaque envelopes were consecutively numbered and centrally stored in the delivery suite.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskWomen would be aware of allocation. None of the midwives involved in the postnatal care of women participating in the trial was aware of the original trial allocation.

Incomplete outcome data (attrition bias)
All outcomes
Low riskProtocol deviations: It is reported that 264/296 infants in the late cord clamping group received the actual management allocated and 252/256 received the actual management allocation. 32 deviations (19 cord around neck, 9 asphyxia,1 maternal emergency and 3 others) were reported. All protocol deviation data were included in the groups to which they were originally allocated for the purpose of analysis (ITT).

Loss to follow-up not reported.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear riskData from 100 women recruited to pilot the trial design was subsequently included in the total of 554 women. It is not clear whether the pilot data was unblinded and therefore may have biased the larger trial.

Philip 1973

MethodsRandomised controlled trial, 2-arm trial with individual randomisation.


ParticipantsSetting: 57 women attending an Edinburgh (Scotland, UK) over a 6 month period in 1969.

Inclusion criteria: Women with uncomplicated pregnancy and term infants with no evidence of blood group incompatibility.

Exclusion criteria: Not stated.


InterventionsEarly clamping: immediately after the delivery of the baby’s buttocks (usually achieved within 5 secs and never longer than 15 secs). N = 28.

Delayed clamping: more than 10 secs after the doctor or midwife thought that the baby was breathing well (mean time 94 secs after birth). N = 29.

In both groups the baby was placed approximately 15 cm below the perineum.


OutcomesApgar score at 5 minutes, birthweight, cord blood hematocrit, bilirubin, haptoglobin, reticulocyte count and infant blood at 24 and 72 hours.


NotesFor continuous outcomes mean and SE were reported. We calculated the SD.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described. “Infants were randomly selected for one of two methods of cord clamping”.

Allocation concealment (selection bias)Unclear riskNot described. “Infants were randomly selected for one of two methods of cord clamping”.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskIt was not clear that all women randomised were accounted for. There were missing data for some outcomes and this was not balanced across groups.                                                   

Selective reporting (reporting bias)Unclear riskAssessment from published study report only.

Other biasLow riskNo other bias apparent. Very little information was provided on study methods. Groups appeared comparable.

Saigal 1972

MethodsRandomised controlled trial (no details of randomisation method).


Participants45 term infants born in 2 hospitals in Montreal, Canada.

Full-term infants 38 to 42 weeks' gestation, vaginal births.

Exclusion criteria: infants of diabetic mothers, malformed infants, infants who developed systemic infections, erythroblastic infants and infants who were small for date (below third percentile for gestational age).


InterventionsImmediate cord clamping - within 5 secs, median 2 secs (n = 15).
Clamping at 1 minute - held low, 30 cm below perineum (n = 15).

All women: oxytocic agents were given only after the cord was clamped.

No phototherapy was given for jaundice.


OutcomesInfant: venous haematocrit, cord haematocrit, blood volume, red cell blood volume, plasma volume, bilirubin.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"assigned prior to delivery according to a randomised study protocol" but no further details given.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses to follow-up or deviation from protocol not reported.

Selective reporting (reporting bias)Unclear riskAssessment from published study report only.

Other biasUnclear riskLittle information on study methods.

Spears 1966

MethodsRandomised controlled trial (no details of randomisation method).


Participants379 women who gave birth vaginally to a term infant weighing greater than 2500 g at the Los Angeles County General Hospital USA.


InterventionsEarly cord clamping was defined as within 1 minute after birth (60% were clamped within 30 secs) (n = 192).
Late cord clamping was defined as clamping as at 3 minutes post birth. In both instances, the infant was held level with the mother's perineum while the cord was cut (n = 187).

No mention of whether or when the mother received any uterotonic agent.


OutcomesInfant: Apgar scores, respiratory distress.


NotesNo maternal outcomes reported that were of relevance to this review.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomly allocated to early or late cord clamping group upon entering the delivery room.No further information

Allocation concealment (selection bias)Unclear riskNo description of how the allocation process was decided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo description of how or whether there was blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot reported.

Selective reporting (reporting bias)Unclear riskAssessment from published study report: neonatal deaths not reportedly by group.

Other biasUnclear riskLittle information on study methods.

van Rheenen 2007

MethodsRandomised controlled trial.


ParticipantsFull-term pregnant women giving birth in hospital.

105 randomised (50 to early and 55 to late cord clamping) - 45 and 46 analysed.

Exclusion criteria: before randomisation: twin pregnancy; history of PPH; gestational diabetes; pre-eclampsia.
After randomisation: placental separation before birth; caesarean section; tight nuchal cord necessitating early cutting; need for neonatal resuscitation; major congenital abnormalities.

Infants who weighed less than 2500 g or with gestational age less than 37 weeks, were excluded.

Setting: hospital in Zambia (malaria-endemic area).


InterventionsImmediate cord clamping within 20 secs of birth (n = 45)
[mean 15 [SD 8] secs].

Cord clamped after cord stopped pulsating (n = 46)
[mean 305 [SD 136] secs].

After vaginal birth all infants were placed between the legs of the mother (about 10 cm below the vaginal introitus) until the cord was clamped.

Intramuscular oxytocin was given to mothers after clamping of the cord.


OutcomesInfant: haemoglobin change from cord values; proportion of anaemic infants at 4 months after birth; duration infants remained free of anaemia (up to 6 months); adverse effects of delayed cord clamping in infants (packed cell volume changes 1 day postpartum; clinical signs of hyperviscosity syndrome or hyperbilirubinaemia) and mothers (haemoglobin change 1 day after birth, blood loss in third stage of labour); birthweight; jaundice; jaundice requiring phototherapy; ZPP levels; blood glucose; malaria; exclusive breastfeeding; infant mortality - 4 deaths (but not reported by early or late cord clamping group).


NotesAnaemia = haemoglobin concentration more than 2 SDs below the mean of similarly aged infants from an iron-supplemented USA reference population not exposed to malaria (9.4 g/dL at 2 months, 10.3 at 4 months and 10.5 at 6 months).
Fetal anaemia = cord haemoglobin < 12.5 g/dL.
Maternal anaemia = haemoglobin < 11 g/dL.
Iron deficiency = ZPP levels above 80 µmol/mol haem for infants and adults.
Iron-deficiency anaemia in mothers and infants = combination of ZPP above the cut-off level, together with haemoglobin more than 2 SD below the reference mean (and mean cell haemoglobin concentration below the cutoff level for 2-month follow-up).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskSequentially numbered opaque sealed envelopes with unpredictable allocation code.

Allocation concealment (selection bias)Low riskSequentially numbered opaque sealed envelopes with unpredictable allocation code.

Blinding (performance bias and detection bias)
All outcomes
Unclear risk"partially blinded" study; "one of the investigators… monitored the delivery procedure and was therefore not blinded to treatment assignment".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses to follow-up: early group: 8/45 (4 at 2 months, 2 more at 4 months, 2 more at 6 months - 6 moved, 1 died, 1 refused further participation).
Late group: 11/46 (3 at 2 months, 4 more at 4 months, 4 more at 6 months - 6 moved, 3 died, 2 refused further participation).
Postrandomisation exclusions: 5/50 in the early group (1 low birthweight, 1 unexpected twin, 1 tight nuchal cord, 1 need for resuscitation, 1 refused further participation), 9/55 in the late group (2 low birthweight, 1 major congenital abnormalities, 2 unexpected twins, 3 tight nuchal cords, 1 need for resuscitation).

Selective reporting (reporting bias)Unclear riskAssessment from published study report only.

Other biasLow riskNot apparent.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Abdel Aziz 1999Quasi-randomised.

Begley 1990This is a comparison of active versus expectant management of the third stage of labour and so is included in the Cochrane review of this topic.

Botha 1968No mention of randomisation and allocation process not described.

Buckels 1965No mention of randomisation and allocation process not described.

Colozzi 1954No mention of randomisation and allocation process not described.

Daily 1970Quasi-randomised - "every other child has early clamping and the others late clamping".

De Paco 2011This was not a randomised trial, allocation to groups was alternate (quasi-randomised).

Duckman 1953No mention of randomisation and allocation process not described.

Dunn 1966It was not clear that this was a randomised trial. It was stated that women were selected at random and then divided into two equal groups (i.e. random selection rather than random allocation).

Emmanouilides 1971No mention of randomisation and allocation process not described.

Erickson-Owens 2012RCT compares early cord clamping with cord milking (not delayed cord clamping).

Erkkola 1984No mention of randomisation and allocation process not described.

Grajeda 1997Quasi-randomised.

Greenberg 1967No mention of randomisation and allocation process not described.

Johansen 1971Quasi-randomised: control group comprised mothers born on odd dates; experimental group comprised mothers born on even dates.

Kemp 1971Quasi-randomised: allocation method open to bias; "patients were allocated according to age: those whose age was an odd number became the group for abdominal manipulation, and those whose age was an even number formed the cord traction group".

Khan 1997This is a comparison of active versus expectant management of the third stage of labour and so is included in the Cochrane review of this topic.

Kliot 1984No mention of randomisation and allocation process not described.

Lanzkowsky 1960This was not a randomised trial. Women in labour were admitted alternately to two different labour wards.

Linderkamp 1992No mention of randomisation and allocation process not described.

Navaneethakrishnan 2010This was not a trial of early verus delayed cord clamping. In this study rhesus negative women in labour were randomised either to have immediate cord clamping and the cord remained clamped until placental delivery versus immediate cord clamping, then the cord was cut and unclamped on the maternal side to allow blood from the placenta to drain off. The purpose was to see whether this reduced feto-maternal transfusion to the rhesus negative mother. Analysis was not performed where the baby was also rhesus negative.

Nelle 1996No mention of randomisation and allocation process not described.

Newton 1961Quasi-randomised: allocation method by rotation.

Prendiville 1988This is a comparison of active versus expectant management of the third stage of labour and so is included in the Cochrane review of this topic.

Rogers 1998This is a comparison of active versus expectant management of the third stage of labour and so is included in the Cochrane review of this topic.

Schindler 1981This study compared clamped and unclamped cord management rather than early versus late timing of cord clamping. Note that although the full paper was in German, a translator was available; it was determined from the English abstract that this study could not be included.

Siddall 1953Quasi-randomised: "in the first half of the experiment the boys cords were milked, while 50 girls had prompt clamping and ligation at delivery. The sexes were reversed for the second 100".

Sorrells-Jones 1982It was not clear how many women were randomised to each group in this study comparing the Leboyer method with routine care. More than half of the sample were excluded post-randomisation. Women in the intervention group received a package of care which included delayed cord clamping along with other interventions and the impact of cord clamping is not clear.

Taylor 1963Quasi-randomised: allocation method by rotation.

Terry 1970Quasi-randomised: allocation method by alternation.

Thilaganathan 1993This is a comparison of active versus expectant management of the third stage of labour and so is included in the Cochrane review of this topic.

Walsh 1968No mention of randomisation and allocation process not described.

Walsh 1969No mention of randomisation and allocation process not described.

Whipple 1957Allocation method, by rotation, open to bias.

Wu 1960Quasi-randomised: allocation method by alternation.

Yao 1971No mention of randomisation and allocation process not described.

Yao 1977It was not clear that this was an RCT. No mention of random allocation to groups. Study concerned with effects of timing of cord clamping on systolic time intervals of the newborn infant

 
Characteristics of studies awaiting assessment [ordered by study ID]
Jaleel 2009

MethodsNot clear.

Participants200 women admitted in labour to a hospital in Karachi.

InterventionsGroup 1: umbilical cord clamped immediately after birth.

Group 2: umbilical cord clamped after cessation of pulsation.

OutcomesNewborn haemoglobin and bilirubin.

NotesWe are awaiting further information on the methods for this study; it was not clear that there was random allocation to groups. More than half of the sample were post-randomisation exclusions and the remaining sample did not appear to be random (for example 65% of the babies were male).

It is stated that is a randomised trial but the authors also state:

“447 deliveries were conducted in the Department. Problems were encountered as patients at Lyari General Hospital tend to leave early after normal deliveries and therefore, obtaining the second blood sample was difficult. Patients with incomplete data were excluded from the study. Finally, 200 patients were included, 100 in each group.”

Li 2012

MethodsRCT.

Participants158 mother-infant pairs.

InterventionsEarly cord clamping (15 seconds) versus late cord clamping (1 minute).

OutcomesInfant iron stores at 4 months.

NotesRequires translation.

Nardozza 2012

MethodsRCT reported in brief abstract.

Participants50 women giving birth in a hospital in Brazil (not clear).

InterventionsImmediate cord clamping versus spontaneous draining of the cord before clamping (not clear).

OutcomesFetal blood cells entering maternal circulation.

NotesThis study was reported in a brief abstract and there was insufficient information to allow us assess eligibility. We are awaiting publication of a full report of this trial.

Ping 2010

MethodsNot clear. Trial registration with no information on study methods.

ParticipantsAll live births.

InterventionsImmediate (within 10 seconds of birth) umbilical cord clamping versus clamping after the cord has ceased pulsing.

OutcomesInfant haemoglobin at one month.

NotesHainan Medical College, China. Chief investigator Professor Hua Shao Ping. We will assess eligibility once findings are published.

 
Characteristics of ongoing studies [ordered by study ID]
Beal 2006

Trial name or titleTiming of cord clamping and neonatal haemoglobin - NCT00371228.

Methods

Participants150 women presenting for vaginal birth at Tulsa Regional Medical Centre, Oklahoma, USA.

Interventions1) Clamping of umbilical cord within 6 seconds of delivery of the fetal shoulders.
2) Clamping the cord after a palpable pulse has ceased, or after 10 minutes.

OutcomesNeonatal haemoglobin.

Starting dateSeptember 2006.

Contact informationJohn M Beal;
Sarah J McCoy, Oklahoma State University Center for Health Sciences
email: sjmccoy98@aol.com

Notes

Hanson 2012

Trial name or titleEffect of delayed cord clamping on the haemoglobin levels of term newborn Aboriginal communities: A pilot randomised trial.

MethodsProposed pilot RCT.

Participants72 Aboriginal women at 36-42 weeks' gestation with uncomplicated vaginal or caesarean birth.

InterventionsDelayed cord clamping until pulsation ceases or after 3 minutes with baby held below the level of the placenta verus standard care (immediate cord clamping).

OutcomesInfant haemoglobin at time of hospital discharge, neonatal morbidity, Apgar score at 5 minutes, neonatal death.

Starting dateStarting date not clear. Proposed end date 29.02.12.

Contact informationmelanie.hanson@menzies.edu.au

NotesProposed study reported in a brief conference abstract.

 
Comparison 1. Early versus late cord clamping

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Severe PPH/blood loss 1000 mL or more52066Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.65, 1.65]

    1.1 Uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.16 [0.46, 2.96]

    1.2 Uterotonic at, or after, clamping
3956Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.57, 1.95]

    1.3 Use of uterotonic not specified
2630Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.29, 2.49]

 2 Neonatal death2381Risk Ratio (M-H, Fixed, 95% CI)0.37 [0.04, 3.41]

 3 PPH/blood loss 500 mL or more52260Risk Ratio (M-H, Fixed, 95% CI)1.17 [0.94, 1.44]

    3.1 Uterotonic before clamping
21032Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.74, 1.67]

    3.2 Uterotonic at, or after, clamping
3956Risk Ratio (M-H, Fixed, 95% CI)1.22 [0.90, 1.65]

    3.3 Use of uterotonic not specified
1272Risk Ratio (M-H, Fixed, 95% CI)1.13 [0.73, 1.74]

 4 Mean blood loss (mL)21345Mean Difference (IV, Fixed, 95% CI)5.11 [-23.18, 33.39]

    4.1 Uterotonic before clamping
1480Mean Difference (IV, Fixed, 95% CI)22.0 [-40.16, 84.16]

    4.2 Uterotonic at, or after, clamping
2865Mean Difference (IV, Fixed, 95% CI)0.70 [-31.06, 32.46]

 5 Maternal haemoglobin (g/dL) 24 to 72 hours postpartum31128Mean Difference (IV, Fixed, 95% CI)-0.12 [-0.30, 0.06]

    5.1 Uterotonic before clamping
1480Mean Difference (IV, Fixed, 95% CI)0.0 [-0.31, 0.31]

    5.2 Uterotonic at, or after, clamping
1483Mean Difference (IV, Fixed, 95% CI)-0.10 [-0.42, 0.22]

    5.3 Use of uterotonic not specified
2165Mean Difference (IV, Fixed, 95% CI)-0.28 [-0.60, 0.04]

 6 Need for blood transfusion21345Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.44, 2.37]

    6.1 Uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.55 [0.26, 9.20]

    6.2 Uterotonic at, or after, clamping
2865Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.34, 2.35]

 7 Need for manual removal of placenta21515Risk Ratio (M-H, Fixed, 95% CI)1.59 [0.78, 3.26]

    7.1 Uterotonic before clamping
21032Risk Ratio (M-H, Fixed, 95% CI)2.17 [0.94, 5.01]

    7.2 Uterotonic at, or after, clamping
1483Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.09, 2.65]

 8 Length of third stage > 30 mins21345Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.55, 2.52]

    8.1 Uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)3.10 [0.32, 29.61]

    8.2 Uterotonic at, or after, clamping
2865Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.44, 2.29]

 9 Length of third stage > 60 mins21345Risk Ratio (M-H, Random, 95% CI)1.11 [0.33, 3.74]

    9.1 Uterotonic before clamping
1480Risk Ratio (M-H, Random, 95% CI)1.03 [0.34, 3.16]

    9.2 Uterotonic at, or after clamping
2865Risk Ratio (M-H, Random, 95% CI)1.68 [0.09, 31.66]

 10 Need for therapeutic uterotonics1963Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.74, 1.20]

    10.1 Uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.10 [0.78, 1.55]

    10.2 Uterotonic at, or after, clamping
1483Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.58, 1.14]

 11 Apgar score < 7 at 5 mins31399Risk Ratio (M-H, Fixed, 95% CI)1.23 [0.73, 2.07]

    11.1 Uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.72 [0.42, 7.13]

    11.2 Uterotonic at, or after, clamping
2540Risk Ratio (M-H, Fixed, 95% CI)1.96 [0.60, 6.42]

    11.3 Use of uterotonic not specified
1379Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.51, 1.85]

 12 Any admission to SCN or NICU41675Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.48, 1.31]

    12.1 Uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.45 [0.47, 4.50]

    12.2 Uterotonic at, or after, clamping
2865Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.37, 1.46]

    12.3 Use of uterotonic not specified
2330Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.20, 1.60]

 13 Respiratory distress3835Risk Ratio (M-H, Random, 95% CI)0.70 [0.22, 2.19]

 14 Jaundice requiring phototherapy72324Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.41, 0.96]

    14.1 Uterotonic before clamping
21032Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.32, 1.11]

    14.2 Uterotonic at, or after, clamping
51112Risk Ratio (M-H, Fixed, 95% CI)0.64 [0.35, 1.18]

    14.3 Use of uterotonic not specified
1180Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.06, 15.74]

 15 Clinical jaundice62098Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.66, 1.07]

    15.1 Uterotonic before clamping
21022Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.62, 1.18]

    15.2 Uterotonic at, or after, clamping
2576Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.57, 1.31]

    15.3 Use of uterotonic not specified
3500Risk Ratio (M-H, Fixed, 95% CI)0.64 [0.29, 1.39]

 16 Polycythaemia51025Risk Ratio (M-H, Fixed, 95% CI)0.39 [0.12, 1.27]

    16.1 Uterotonic at, or after, clamping
3577Risk Ratio (M-H, Fixed, 95% CI)0.38 [0.06, 2.48]

    16.2 Use of uterotonic not specified
2448Risk Ratio (M-H, Fixed, 95% CI)0.40 [0.09, 1.80]

 17 Cord haemoglobin (g/dL)5696Mean Difference (IV, Fixed, 95% CI)0.41 [0.15, 0.66]

    17.1 Uterotonic at, or after, clamping
3531Mean Difference (IV, Fixed, 95% CI)0.48 [0.19, 0.76]

    17.2 Use of uterotonic not specified
2165Mean Difference (IV, Fixed, 95% CI)0.15 [-0.42, 0.71]

 18 Newborn haemoglobin (g/dL)3671Mean Difference (IV, Random, 95% CI)-2.17 [-4.06, -0.28]

    18.1 Uterotonic at, or after, clamping
145Mean Difference (IV, Random, 95% CI)-4.45 [-5.33, -3.57]

    18.2 Use of uterotonic not specified
2626Mean Difference (IV, Random, 95% CI)-1.07 [-2.03, -0.12]

 19 Infant haemoglobin at 24-48 hours (g/dL)4884Mean Difference (IV, Fixed, 95% CI)-1.49 [-1.78, -1.21]

    19.1 Uterotonic at, or after, clamping
2426Mean Difference (IV, Fixed, 95% CI)-1.40 [-1.75, -1.05]

    19.2 Use of uterotonic not specified
2458Mean Difference (IV, Fixed, 95% CI)-1.68 [-2.18, -1.19]

 20 Infant haemoglobin at 3-6 months (g/dL)61115Mean Difference (IV, Random, 95% CI)-0.15 [-0.48, 0.19]

    20.1 Uterotonic at, or after, clamping
2434Mean Difference (IV, Random, 95% CI)0.03 [-0.17, 0.22]

    20.2 Use of uterotonic not specified
4681Mean Difference (IV, Random, 95% CI)-0.26 [-0.79, 0.26]

 21 Low infant haemoglobin at 3-6 months4954Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.79, 1.39]

    21.1 Uterotonic at, or after, clamping
2438Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.67, 1.36]

    21.2 Use of uterotonic not specified
2516Risk Ratio (M-H, Fixed, 95% CI)1.19 [0.74, 1.92]

 22 Infant haematocrit (%)1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    22.1 At 24 hours
1180Mean Difference (IV, Fixed, 95% CI)-4.40 [-5.71, -3.09]

    22.2 At 3-5 months
1160Mean Difference (IV, Fixed, 95% CI)-0.40 [-1.48, 0.68]

 23 Low infant haematocrit (< 45% at 6 hours)1272Risk Ratio (M-H, Fixed, 95% CI)16.18 [2.05, 127.37]

    23.1 Use of uterotonic not specified
1272Risk Ratio (M-H, Fixed, 95% CI)16.18 [2.05, 127.37]

 24 Low infant haematocrit (< 45% at 24-48 hours)1268Risk Ratio (M-H, Fixed, 95% CI)6.03 [2.27, 16.07]

    24.1 Use of uterotonic not specified
1268Risk Ratio (M-H, Fixed, 95% CI)6.03 [2.27, 16.07]

 25 Infant iron deficiency at 3-6 months51152Risk Ratio (M-H, Random, 95% CI)2.65 [1.04, 6.73]

    25.1 Uterotonic at, or after, clamping
2425Risk Ratio (M-H, Random, 95% CI)2.73 [0.19, 40.19]

    25.2 Use of uterotonic not specified
3727Risk Ratio (M-H, Random, 95% CI)2.91 [1.18, 7.20]

 26 Birthweight (g)123139Mean Difference (IV, Random, 95% CI)-101.18 [-157.59, -44.76]

 27 Not breastfeeding on discharge (or later)9Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    27.1 At discharge
41633Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.90, 1.36]

    27.2 At 1 month
1268Risk Ratio (M-H, Fixed, 95% CI)1.10 [1.00, 1.20]

    27.3 At 2 months
184Risk Ratio (M-H, Fixed, 95% CI)0.21 [0.01, 4.24]

    27.4 At 3 months
2144Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.36, 2.42]

    27.5 At 4 months
2391Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.74, 1.04]

    27.6 At 6 months
2430Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.89, 1.11]

 28 Neurodevelopment at 4 months1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    28.1 ASQ total score
1365Mean Difference (IV, Fixed, 95% CI)-1.40 [-7.31, 4.51]

    28.2 ASQ communication score
1365Mean Difference (IV, Fixed, 95% CI)-0.30 [-1.87, 1.27]

    28.3 ASQ gross motor score
1365Mean Difference (IV, Fixed, 95% CI)-0.60 [-2.11, 0.91]

    28.4 ASQ fine motor score
1365Mean Difference (IV, Fixed, 95% CI)-0.90 [-3.10, 1.30]

    28.5 ASQ problem-solving score
1365Mean Difference (IV, Fixed, 95% CI)-1.80 [-3.38, -0.22]

    28.6 ASQ personal-social score
1365Mean Difference (IV, Fixed, 95% CI)2.30 [0.51, 4.09]

 29 Symptoms of infection during first 4 months1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    29.1 Fever
1360Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.64, 1.31]

    29.2 Diarrhoea
1360Risk Ratio (M-H, Fixed, 95% CI)1.12 [0.57, 2.19]

    29.3 Loose stools
1360Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.57, 1.27]

    29.4 Hard stools
1360Risk Ratio (M-H, Fixed, 95% CI)0.78 [0.28, 2.21]

    29.5 Belly ache
1360Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.81, 1.71]

    29.6 Vomiting
1360Risk Ratio (M-H, Fixed, 95% CI)1.38 [0.79, 2.41]

    29.7 Cough
1360Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.72, 1.23]

    29.8 Breathing difficulties
1360Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.40, 1.60]

    29.9 Rhinorrhea/runny nose
1360Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.69, 1.28]

    29.10 Nasal congestion
1360Risk Ratio (M-H, Fixed, 95% CI)1.07 [0.89, 1.27]

    29.11 Otitis
1360Risk Ratio (M-H, Fixed, 95% CI)0.70 [0.12, 4.12]

    29.12 Rash
1360Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.59, 1.60]

    29.13 Crying
1360Risk Ratio (M-H, Fixed, 95% CI)1.37 [0.95, 1.96]

    29.14 Tiredness
1360Risk Ratio (M-H, Fixed, 95% CI)1.17 [0.71, 1.93]

    29.15 Visit to paediatrician
1360Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.56, 1.23]

    29.16 Visit to other doctor
1360Risk Ratio (M-H, Fixed, 95% CI)1.19 [0.60, 2.37]

    29.17 Antibiotics
1360Risk Ratio (M-H, Fixed, 95% CI)1.36 [0.61, 3.02]

    29.18 Admitted to hospital
1360Risk Ratio (M-H, Fixed, 95% CI)1.46 [0.67, 3.21]

 
Table 1. Infant iron deficiency and ferritin at 3-6 months

STUDY Iron deficiencyFerritin

Al-Tawil 2012Data collected at 3-5 months

Mean cell volume < 73 fL

Early clamping group 4/78

Late clamping group 2/82

P = 0.43

Transferrin saturation levels below 10%

Early clamping group 11/78

Late clamping group 8/82

P = 0.62
At 3-5 months. Defined as serum ferritin < 20 µg/L

Early clamping group 12/78

Late clamping group 2/82

P <0.001

Also reported mean (SD) ferritin

Early clamping group (n = 78) mean 228 (SD 147)

Late clamping group (n = 82) mean 430 (SD 132) P <0.001

Andersson 2011Defined as 2 or more indicators outside reference ranges (low ferritin, low mean cell volume, low transferrin saturation, high transferrin receptors)

At 4 months

Early clamping group 10/175

Late clamping group 1/172

P = 0.01

 

Also reported mean iron (µmol/L)

At 4 months

Early clamping group (n = 175) 9.3 (SD 2.9)

Late clamping group (n = 172) 10.2 (SD 3.0)

P = 0.007
Geometric mean and range

 

At 4 months

 

Early (n = 175) 81 (6-670)

Late ( n = 168) 117 (20-880)

P < 0.001

Cernadas 2006Iron deficiency anaemia at 6 months  (defined as Hb < 10.5 g/dL and ferritin < 9 µg/L)

15 second group 6/86

1-minute group 3/84

3-minute group 2/84
Ferritin < 9 µg/L at 6 months

15 second 13/86

1 minute 10/83

3 minutes 6/83

 

Ferritin geometric mean at 6 months

15 seconds (n = 86) 20.9 (SD 26.3)

1 minute (n = 83) 25.5 (SD 26.0)

3 minute ( n = 83) 33.2 SD 36.8)

Chaparro 2006Iron deficiency at 4-6 months (defined as ferritin < 9 µg/L)

Early clamping 12/154

Late clamping 3/ 161

P = 0.02
Ferritin µg/L at 4-6 months. Mean and SD

 

Early clamping (n = 154) 34.9 (32.2)

Late clamping (n = 161) 46.7 (37.7)

P = 0.001

Geethanath 1997Not reportedFerritin µg/mL geometric mean at 3 months (dispersion statistic not clear)

Early clamping group (n = 48) 55.7 (3.7)

Late clamping group (n = 59) 73.6 (3.1)

Difference not significant.

Gupta 2002Not reportedFerritin µg/L geometric mean, median and range at 3 months.

Early clamping  (n = 29) geometric mean 73.04, median and range 80 (15 to 180)

Late clamping  (n = 29) geometric mean 118.39, median and range 105 (30 to 500)

P = 0.02

van Rheenen 2007Iron deficiency anaemia (defined as zinc-protoporphyrin (ZPP) >80 µmol/mol haem and Hb < 10.3)

At 4 months

Immediate clamping 14/39

Delayed clamping 6/39

NS

At 6 months

Immediate clamping 17/37

Delayed clamping 17/35

NS

 

Iron deficiency (ZPP > 80 µmol/mol haem)

At 4 months

Delayed clamping 27/39

Immediate clamping 28/39

NS

 

At 6 months

Delayed clamping 27/35

Immediate clamping 28/37

NS

 
 

 fL: femtolitre
Hb: haemoglobin
SD: standard deviation