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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

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 8 JUL 2009

Assessed as up-to-date: 30 DEC 2007

DOI: 10.1002/14651858.CD004074.pub2

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How to Cite

McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD004074. DOI: 10.1002/14651858.CD004074.pub2.

Author Information

  1. 1

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

  2. 2

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

*Susan J McDonald, Midwifery Professorial Unit, La Trobe University/Mercy Hospital for Women, Level 4, Room 4.071, 163 Studley Road, Heidelberg, Victoria, 3084, Australia. s.mcdonald@latrobe.edu.au. smcdonald3@mercy.com.au.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 8 JUL 2009

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Characteristics of included studies [ordered by study ID]
Cernadas 2006
MethodsRandomised controlled trial.
Computer-generated random numbers - stratified by hospital and then by mode of birth within each hospital. Variable length blocks were used.
Allocation 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: paediatricians assessing the outcomes were unaware of the assigned interventions.
Nature of the intervention meant that others could not be blinded.

Losses to follow up: primary outcome was not measured in:
early 3/93; late 1 min 1/91; late 3 min 0/92.
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 seconds of birth).
n = 93 [88/93 received the intervention - no cause given for 5 changes].
2. Cord clamping at 1 min 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 mins 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 apnea; 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
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate




Chaparro 2006
MethodsRandomised controlled trial.
Blocks of 4 generated by random digital generator in Microsoft Excel. Numbered index cards with allocation were sealed in numbered opaque envelopes ordered sequentially.
Blinding: no mention of blinding.
Losses 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.
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 mins 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
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate




Emhamed 2004
MethodsRandomised controlled trial. Consecutive allocation of opaque envelopes.
Blinding: not stated.
Losses 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.
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), polycythemia, hyperviscosity and jaundice.
Notes
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear




Geethanath 1997
MethodsAllocation by opaque, sealed envelopes.
Blinding: not reported.
Losses to follow up: not reported.
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 completion of birth.
Infant: cord blood at birth and and venous blood sample at 3 months for ferritin and haemoglobin estimation.
Notes
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear




Gupta 2002
MethodsAllocation by opaque sealed envelopes, with computer-generated random number sequences.
Blinding: not stated.
Losses to follow up: at 3 months, 58 (57%) of the original 102 mother-infant pairs were available, 29 pairs in each group.
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.
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
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear




McDonald 1996
MethodsRandomisation: list of computer-generated random numbers.
Opaque, sealed, sequentially numbered envelopes kept at a central location in the delivery ward.
Blinding: see notes.
Losses 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).
ParticipantsAll women attending the antenatal clinic at King Edward Memorial Hospital, 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 mins 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 (ie not within 30 seconds).
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 mins and > 60 mins); need for therapeutic uterotonics; evacuation of retained products; inversion of the uterus; length of hospital stay.
Neonatal: Apgar score < 6 at 5 mins; 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; submission is planned in 2008.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate




Nelson 1980
MethodsRandomisation: "assigned randomly" - no further details provided.
Blinding: 2nd observer blinded for Brazelton Neonatal Behavioural Assessment Scale, infant Bayley Scales of Infant Development assessed blind.
Losses to follow up: 1/55 (dropped out from conventional (early clamping) group.
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 min 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
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear




Oxford Midwives 1991
MethodsRandomisation: generation by random-number tables (simple unblocked and unstratified); sealed opaque envelopes were consecutively numbered and centrally stored in the delivery suite.
Participants554 women.

Setting: large teaching hospital in Oxford, UK.
InterventionsEarly clamping (as soon as possible after the birth) or late clamping (3 mins 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.
Notes
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate




Saigal 1972
MethodsRandomisation: "assigned prior to delivery according to a randomised study protocol" but no further details given.
Blinding: not reported.
Losses to follow up: not stated.
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 min - 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
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear




Spears 1966
MethodsRandomly allocated to early or late cord clamping group upon entering the delivery room.
No description of how the allocation process was decided.
Participants379 women who gave birth vaginally to a term infant weighing greater than 2500 gm at the Los Angeles County General Hospital USA.
InterventionsEarly cord clamping was defined as within 1 min after birth (60% were clamped within 30 secs) (n = 192).
Late cord clamping was defined as clamping as at 3 mins 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
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear




van Rheenen 2007
MethodsRandomisation: sequentially numbered opaque sealed envelopes with unpredictable allocation code.
Blinding: "partially blinded" study; "one of the investigators… monitored the delivery procedure and was therefore not blinded to treatment assignment".
Losses 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).
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 = Hb 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 umol/mol haem for infants and adults.
Iron-deficiency anaemia in mothers and infants = combination of ZPP above the cutoff level, together with Hb 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
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate
 IUGR: intrauterine growth retardation
mins: minutes
NICU: neonatal intensive care unit
PDA: patent ductus arteriosus
PPH: postpartum haemorrhage
SD: standard deviation
secs: seconds
ZPP: zinc protoporphyrin


 
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".
Duckman 1953No mention of randomisation and allocation process not described.
Emmanouilides 1971No mention of randomisation and allocation process not described.
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.
Linderkamp 1992No mention of randomisation and allocation process not described.
Nelle 1996No mention of randomisation and allocation process not described.
Newton 1961Quasi-randomised: allocation method by rotation.
Philip 1973No clinical outcomes relevant to this review were measured.
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.
Saigal 1981No clinical outcomes relevant to this review were measured.
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 1982No clinical outcomes relevant to this review were measured.
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 1977No clinical outcomes relevant to this review were measured.


 
Characteristics of ongoing studies [ordered by study ID]
Beal 2006
Trial name or titleTiming of cord clamping and neonatal hemoglobin - 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


 
Comparison 1. Early versus late cord clamping
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 PPH/blood loss 500 ml or more41878Risk Ratio (M-H, Fixed, 95% CI)1.22 [0.96, 1.55]
    1.1 uterotonic before clamping
21032Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.74, 1.67]
    1.2 uterotonic at, or after, clamping
2574Risk Ratio (M-H, Fixed, 95% CI)1.42 [0.95, 2.14]
    1.3 use of uterotonic not specified
1272Risk Ratio (M-H, Fixed, 95% CI)1.13 [0.73, 1.74]
 2 Severe PPH/blood loss 1000 ml or more41684Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.48, 1.49]
    2.1 uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.16 [0.46, 2.96]
    2.2 uterotonic at, or after, clamping
2574Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.22, 1.59]
    2.3 use of uterotonic not specified
2630Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.29, 2.49]
 3 Mean blood loss (ml)1963Mean Difference (IV, Fixed, 95% CI)6.36 [-34.94, 47.66]
    3.1 uterotonic before clamping
1480Mean Difference (IV, Fixed, 95% CI)22.0 [-40.16, 84.16]
    3.2 uterotonic at, or after, clamping
1483Mean Difference (IV, Fixed, 95% CI)-6.0 [-61.25, 49.25]
 4 Maternal haemoglobin (g/dL) 24 to 72 hours postpartum31128Mean Difference (IV, Fixed, 95% CI)-0.12 [-0.30, 0.06]
    4.1 uterotonic before clamping
1480Mean Difference (IV, Fixed, 95% CI)Not estimable
    4.2 uterotonic at, or after, clamping
1483Mean Difference (IV, Fixed, 95% CI)-0.10 [-0.42, 0.22]
    4.3 use of uterotonic not specified
2165Mean Difference (IV, Fixed, 95% CI)-0.28 [-0.60, 0.04]
 5 Need for blood transfusion1963Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.20, 3.15]
    5.1 uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.55 [0.26, 9.20]
    5.2 uterotonic at, or after, clamping
1483Risk Ratio (M-H, Fixed, 95% CI)0.20 [0.01, 4.06]
 6 Need for manual removal of placenta21515Risk Ratio (M-H, Fixed, 95% CI)1.59 [0.78, 3.26]
    6.1 uterotonic before clamping
21032Risk Ratio (M-H, Fixed, 95% CI)2.17 [0.94, 5.01]
    6.2 uterotonic at, or after, clamping
1483Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.09, 2.65]
 7 Length of third stage > 30 mins1963Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.29, 3.41]
    7.1 uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)3.10 [0.32, 29.61]
    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 > 60 mins1963Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.32, 2.04]
    8.1 uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.34, 3.16]
    8.2 uterotonic at, or after clamping
1483Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.09, 2.65]
 9 Need for therapeutic uterotonics1963Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.74, 1.20]
    9.1 uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.10 [0.78, 1.55]
    9.2 uterotonic at, or after, clamping
1483Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.58, 1.14]
 10 Maternal ferritin (ug/L)1107Mean Difference (IV, Fixed, 95% CI)9.10 [7.86, 10.34]
    10.1 use of uterotonic not specified
1107Mean Difference (IV, Fixed, 95% CI)9.10 [7.86, 10.34]
 11 Apgar score < 7 at 5 mins21342Risk 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
1483Risk 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 Admission to SCN or NICU31293Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.56, 1.90]
    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
1483Risk Ratio (M-H, Fixed, 95% CI)1.57 [0.52, 4.72]
    12.3 use of uterotonic not specified
2330Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.20, 1.60]
 13 Admission for respiratory distress21008Risk Ratio (M-H, Random, 95% CI)1.01 [0.18, 5.75]
    13.1 uterotonic before clamping
1480Risk Ratio (M-H, Random, 95% CI)0.41 [0.08, 2.11]
    13.2 uterotonic at, or after, clamping
2528Risk Ratio (M-H, Random, 95% CI)2.45 [0.48, 12.50]
 14 Respiratory distress1379Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.65, 1.89]
    14.1 use of uterotonic not specified
1379Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.65, 1.89]
 15 Jaundice requiring phototherapy51762Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.38, 0.92]
    15.1 uterotonic before clamping
21032Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.32, 1.11]
    15.2 uterotonic at, or after, clamping
4730Risk Ratio (M-H, Fixed, 95% CI)0.58 [0.31, 1.11]
 16 Clinical jaundice51918Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.66, 1.07]
    16.1 uterotonic before clamping
21022Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.62, 1.18]
    16.2 uterotonic at, or after, clamping
2576Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.57, 1.31]
    16.3 use of uterotonic not specified
2320Risk Ratio (M-H, Fixed, 95% CI)0.64 [0.29, 1.39]
 17 Polycythaemia3463Risk Ratio (M-H, Fixed, 95% CI)0.39 [0.12, 1.27]
    17.1 uterotonic at, or after, clamping
2195Risk Ratio (M-H, Fixed, 95% CI)0.38 [0.06, 2.48]
    17.2 use of uterotonic not specified
1268Risk Ratio (M-H, Fixed, 95% CI)0.40 [0.09, 1.80]
 18 Cord haemoglobin (g/dL)4314Mean Difference (IV, Fixed, 95% CI)0.42 [0.03, 0.80]
    18.1 uterotonic at, or after, clamping
2149Mean Difference (IV, Fixed, 95% CI)0.66 [0.13, 1.19]
    18.2 use of uterotonic not specified
2165Mean Difference (IV, Fixed, 95% CI)0.15 [-0.42, 0.71]
 19 Newborn haemoglobin (g/dL)3671Mean Difference (IV, Random, 95% CI)-2.17 [-4.06, -0.28]
    19.1 uterotonic at, or after, clamping
145Mean Difference (IV, Random, 95% CI)-4.45 [-5.33, -3.57]
    19.2 use of uterotonic not specified
2626Mean Difference (IV, Random, 95% CI)-1.07 [-2.03, -0.12]
 20 Infant haemoglobin at 24-48 hours (g/dL)2382Mean Difference (IV, Fixed, 95% CI)-1.34 [-1.80, -0.88]
    20.1 uterotonic at, or after, clamping
1104Mean Difference (IV, Fixed, 95% CI)-1.40 [-2.17, -0.63]
    20.2 use of uterotonic not specified
1278Mean Difference (IV, Fixed, 95% CI)-1.31 [-1.88, -0.74]
 21 Infant haemoglobin at 2-4 months (g/dL)3256Mean Difference (IV, Random, 95% CI)-0.30 [-1.25, 0.65]
    21.1 uterotonic at, or after, clamping
191Mean Difference (IV, Random, 95% CI)-0.30 [-0.88, 0.28]
    21.2 use of uterotonic not specified
2165Mean Difference (IV, Random, 95% CI)-0.27 [-1.94, 1.39]
 22 Infant haemoglobin at 6 months (g/dL)2447Mean Difference (IV, Fixed, 95% CI)0.03 [-0.17, 0.23]
    22.1 uterotonic at, or after, clamping
191Mean Difference (IV, Fixed, 95% CI)0.40 [-0.35, 1.15]
    22.2 use of uterotonic not specified
1356Mean Difference (IV, Fixed, 95% CI)Not estimable
 23 Infant haematocrit < 45% at 6 hours1272Risk 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 Infant haematocrit < 45% at 24-48 hours1268Risk 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 haemoglobin > 2 SDs below 10.3 g/dL at 4 months191Risk Ratio (M-H, Fixed, 95% CI)1.84 [0.96, 3.54]
    25.1 uterotonic at, or after, clamping
191Risk Ratio (M-H, Fixed, 95% CI)1.84 [0.96, 3.54]
 26 Infant haemoglobin at 6 months2447Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.75, 1.48]
    26.1 > 2 SD below 10.5 g/dL: uterotonic at, or after, clamping
191Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.61, 1.43]
    26.2 < 12.2 g/dL: use of uterotonic not specified
1356Risk Ratio (M-H, Fixed, 95% CI)1.17 [0.70, 1.96]
 27 Infant ferritin (ug/L)2Mean Difference (IV, Fixed, 95% CI)Subtotals only
    27.1 at 3 months: use of uterotonic not specified
1107Mean Difference (IV, Fixed, 95% CI)-17.90 [-19.21, -16.59]
    27.2 at 6 months: use of uterotonic not specified
1315Mean Difference (IV, Fixed, 95% CI)-11.80 [-19.53, -4.07]
 28 Exclusive breastfeeding5Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
    28.1 at discharge: uterotonic before clamping
1480Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.95, 1.08]
    28.2 at discharge: uterotonic at, or after, clamping
1483Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.97, 1.10]
    28.3 1 month: use of uterotonic not specified
1268Risk Ratio (M-H, Fixed, 95% CI)1.10 [1.00, 1.20]
    28.4 2 months: use of uterotonic not specified
1302Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.75, 1.28]
    28.5 3 months: use of uterotonic not specified
2144Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.90, 1.13]
    28.6 4 months: use of uterotonic not specified
1313Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.76, 1.30]
    28.7 6 months: use of uterotonic not specified
1358Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.73, 1.33]
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