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Table 1 Study characteristics

From: Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis

No.

Author/Year

Country

Participants

Participants, n

Intervention / Timing

Control / Timing

Outcomes

Umbilical cord milking

 1

Atia 2022

Saudi Arabia

Inclusion: preterm (24.0–34.6 weeks), singleton

Exclusion: multifetal pregnancy, diagnosed congenital anomalies, fetal anaemia, considerable antepartum haemorrhage, category III cardiotocography tracing

200

(Intervention: 100, Control:100)

Cord was milked 4–5 times, at 10 cm/s

Cord was clamped at 45-60 s

Length of hospital stay, neonatal mortality

 2

Chellappan 2022

India

Inclusion: preterm (27 – 32 weeks)

Exclusion: monochorionic diamniotic twins, intrauterine growth restriction, hydrops fetalis, major congenital anomalies

179

(Intervention: 93; Control: 86)

Cord was milked 3 times for 10-20 s

Early cord clamping (undefined)

Length of hospital stay,

neurodevelopmental outcomes at 6–12 months corrected age

(Moderate to severe disability), neurological examination, Trivandrum development screening chart; Developmental assessment scale for Indian infants

 3

Elimian 2014

USA

Inclusion: singleton, preterm (24 – 34.0 weeks)

Exclusion: major fetal structural or chromosomal abnormalities, multiple gestations, maternal diabetes, intrauterine growth restriction, non-reassuring fetal heart tracings

200 (Intervention: 99; Control: 101)

Cord was clamped after 30 s, and milked 3–4 times

Cord was clamped within 5 s of birth

Neonatal mortality

 4

El-Naggar 2022

Canada

Inclusion: singleton, preterm (24—30.6 weeks)

Exclusion: monochorionic twins, major congenital anomalies, placental abruption, fetal anaemia, intention to withhold resuscitation

65

(Intervention:34; Control: 31)

Cord was milked three times, speed 10 cm/s

Cord was clamped within 10 s of birth

Neurodevelopmental outcomes at 36 months corrected age

(Bayley Scales of Infant and Toddler development – III), neurological examination, Gross Motor Functional Classification System

 5

El-Naggar 2018

Canada

Inclusion: singleton, preterm (24—30.6 weeks)

Exclusion: monochorionic twins, major congenital anomalies, placental abruption, fetal anaemia, intention to withhold resuscitation

73

(Intervention: 37; Control: 36)

Cord was milked three times, speed 10 cm/s

Cord was clamped within 10 s of birth

Neonatal mortality, length of hospital stay

 6

Erickson-Owens 2012

USA

Inclusion: singleton, term (> 37 weeks); caesarean delivery

Exclusion: maternal medical and obstetric

complications, severe anaemia, clotting disorders, suspected intrauterine growth restriction, smoking in pregnancy, non-English speaker, infant with confirmed diagnosis of intrauterine growth restriction, serious congenital anomalies

24

(Intervention: 12; Control: 12)

Cord was milked five times before clamping

Cord was clamped within 10 s of birth

Admission to NICU

 7

Hosono 2007

Japan

Inclusion: singleton, preterm (24 – 28.6 weeks) and/or low birth weight (< 2500 g)

Exclusion: multiple births, major congenital anomalies, chromosomal anomalies, hydrops fetalis

40

(Intervention: 20; Control: 20)

Cord was milked 2–3 times at 20 cm/s before being clamped

Cord was clamped immediately after birth

Neonatal mortality

 8

Katheria 2014

USA

Inclusion: singleton, preterm (23 – 31.6 weeks)

Exclusion: imminent delivery, monochorionic multiples, incarcerated mothers, placenta previa, concern for abruptions, refusal to perform the intervention by the obstetrician

60 (Intervention: 30; Control: 30)

Cord was milked at 20 cm over 2 s, repeated twice

Cord was clamped after 14 s (± 9 s)

Neonatal mortality

 9

Katheria 2015

USA

Inclusion: singleton, preterm (23 – 31.6 weeks)

Exclusion: monochorionic multiples, incarcerated mother, placenta previa, concern for abruption, Rh sensitisation, hydrops, congenital anomalies, obstetrician declined to perform the intervention

197 (Intervention: 75; Control: 79)

Cord was milked four times over 2 s, with a 1-2 s pause between milking, then clamped at 20 s after birth

Cord was clamped at least 45 s after birth (42 s ± 12 s)

Neonatal mortality

 10

Katheria 2018

USA

Inclusion: singleton, Preterm (23 – 31.6 weeks)

Exclusion: monochorionic multiples, incarcerated mothers, placenta previa, concern for placental abruption, Rh sensitization, hydrops, congenital anomalies

135

(Intervention: 70; Control: 65)

Cord was milked over 2 s and then repeated 3 additional times

Delayed cord clamping (45-60 s)

Neurodevelopmental outcomes at 22–26 months CA (Bayley Scales of Infant and Toddler development – III, Gross Motor Functional Classification System, neurological examination)

 11

Krueger 2015

USA

Inclusion: singleton, preterm (22 – 31.6 weeks)

Exclusion: fetal anomalies, suspected placental abruption

67

(Intervention: 35; Control: 32)

1/3 – 2/3 of the length of the umbilical cord was stripped between two fingers 4 times, with 4-5 s pause in between, and clamped after 30 s

Cord was clamped at 30 s after birth

Length of hospital stay, neonatal mortality

 12

Kumawat 2022

India

Inclusion: term and late preterm (≥ 34 weeks)

Exclusion: short umbilical cord (i.e., < 25 cm), prolapsed cord, abnormal cord and placenta, Rh-negative mothers, hydrops fetalis, delayed cry after birth, gross congenital malformations

168

(Intervention: 84; Control: 84)

Umbilical cord was cut at 30 s and milked three times at a speed of 10 cm/s

Cord was clamped at 30 s after birth

Admission to NICU

 13

Mangla 2020

India

Inclusion: late preterm and term (35.0 – 42.6 weeks)

Exclusion: fetal hydrops, major congenital malformation, Rh isoimmunization, new-borns born through meconium-stained liquor who were non-vigorous at birth, forceps or vacuum assisted delivery, new-borns born to HIV positive mother, maternal eclampsia

144

(Intervention: 72; Control: 72)

Umbilical cord was milked four times and clamped at 12.9 s (± 0.8 s)

Cord was clamped 60 s after birth

Admission to NICU

 14

Mercer 2016

USA

Inclusion: singleton, preterm (24 – 31.6 weeks)

Exclusion: multiple gestation, prenatally diagnosed major congenital anomalies, severe or multiple maternal illnesses, mothers who were at risk for loss to follow-up

161

(Intervention: 74; Control: 87)

Cord milked once at 30-45 s after birth

Cord was clamped within 10 s of birth

Neurodevelopmental outcomes at 18–22 months

(Bayley Scales of Infant and Toddler development – III: Motor Score only)

 15

Panburana 2020

Thailand

Inclusion: singleton, term (37—42 weeks)

Exclusion: umbilical cord length less than 25 cm or cord abnormality(such as true knots or cord prolapse), multiple gestation, maternal Rh-negative blood group, positive anti-HIV, positive HBsAg, and syphilis infection during pregnancy, antenatal diagnosed major congenital anomalies of foetus or apparent at birth, fetal hydrops and fetal growth restriction, intrapartum fetal non reassuring or fetal distress, non-vigorous neonates, unstable maternal hemodynamic condition, placenta abruption, placenta previa, uterine rupture, declined to participate

168 (Intervention: 84; Control: 84)

Cord was milked 3 times, at 25 cm length, at 10 cm/s with 2 s interval and then clamped

Cord was clamped 60 s after birth

Length of hospital stay

 16/17

Rabe 2011/

Rabe 2016

UK

Inclusion: singleton, preterm (24 – 32.6 weeks)

Exclusion: multiple pregnancies (twins and more), fetal hydrops, rhesus sensitization, major congenital abnormalities

58

(Baseline -Intervention:; Control:)

(2 year FU—Intervention: 22; Control: 17)

(3.5 year FU—Intervention: 18; Control: 11)

Cord was milked four times at a speed of 20 cm/s

Cord was clamped at 30 s after birth

Neonatal mortality, length of hospital stay, glucose concentration (on admission), neurodevelopmental outcomes at 2 years and 3.5 years (Bayley Scales of Infant and Toddler development – III)

 18

Shirk 2019

USA

Inclusion: singleton, preterm (23 – 34.6 weeks)

Exclusion: major and minor congenital anomalies (not including trisomy markers), precipitous delivery that prevented completion of the protocol, placental abruption, uterine rupture, infants known to be at risk of anaemia, patient delivered at outside institution after random assignment. Once enrolled, a patient was excluded if they had a category 3 fetal heart rate tracing or prolonged fetal bradycardia

204

(Intervention: 100; Control: 104)

Milking / stripping of 20 cm of umbilical cord four times, allowing for refill between each milking manoeuvre

Cord was clamped at 60 s after birth

Neonatal mortality

 19

Silahli 2018

Turkey

Inclusion: preterm (≤ 32 weeks)

Exclusion: twin-to-twin transfusion syndrome, fetal and maternal bleeding, dysmorphic features, conotruncal heart disease

75

(Intervention: 38; Control: 37)

Cord was milked at 20 cm, 3 times before clamping

Cord was clamped within 10 s of delivery

Length of hospital stay

 20

Song 2017

Korea

Inclusion: preterm (24 -32.6 weeks)

Exclusion: multiple gestations, rhesus sensitization, fetal hydrops, major fetal anomalies, no consent provided

66 (Intervention: 34; Control: 32)

Cord was milked 4 times at 20 cm/s with a 2 s pause, which took approximately 15-20 s

Cord was clamped immediately after delivery

Length of hospital stay, neonatal mortality

 21

Xie 2022

China

Inclusion: singleton, preterm (< 34 weeks)

Exclusion: postpartum haemorrhage, major congenital anomalies, hydrops fetalis, haemolysis disease, multiple births, SGA infants

253 (Intervention: 121; Control: 132)

Cord was milked for 2 s, repeated four times

Cord was clamped immediately after birth

Neonatal mortality

Delayed cord clamping

 22

Andersson 2011

Sweden

Inclusion: singleton, vaginal delivery, term (37.0 – 41.6 weeks)

Exclusions: serious congenital malformations, syndromes, other congenital diseases that could affect the outcome measures

344 (DCC:170; Control:174)

Cord was clamped at 180 s

Cord was clamped ≤ 10 s

Admission to NICU, Admission to NICU for hypoglycaemia

 23

Andersson 2013

Sweden

Inclusion: singleton, vaginal delivery, term (> 37 weeks)

Exclusion: serious congenital malformations, syndromes, other congenital diseases of the newborn

infant that could affect the outcome measures

365

(DCC: 185; Control: 180)

Cord was clamped at 180 s

Cord was clamped ≤ 10 s

Neurodevelopmental outcomes at 4 months (Ages and Stages Questionnaire)

 24

Andersson 2014

Sweden

Inclusion: singleton, vaginal delivery, term (> 37 weeks)

Exclusion: serious congenital malformations, syndromes or other congenital diseases of the newborn

infant that could affect the outcome measures

340

(DCC: 172; Control: 168)

Cord was clamped at 180 s

Cord was clamped ≤ 10 s

Neurodevelopmental outcomes at 12 months (Ages and Stages Questionnaire)

 25

Andersson 2015

Sweden

Inclusion: vaginal delivery, term (37–41 weeks)

Exclusion: serious congenital malformations, syndromes, other congenital diseases of the newborn

infant that could affect the outcome measures

263

(DCC: 141; Control: 122)

Cord was clamped at 180 s

Cord was clamped ≤ 10 s

Neurodevelopmental outcomes at 48 months (Wechsler Preschool and Primary Scale of Intelligence-III; Ages and Stages Questionnaire -3)

 26

Armanian 2017

Iran

Inclusion: preterm (< 34 weeks)

Exclusion: non-admission to the NICU, twin pregnancy, attending clinician not compliant with the study protocol, parents’ refusal to participate, major congenital anomalies, asphyxia

60

(DCC: 30; Control: 30)

Cord was clamped 30-45 s after birth

Cord was clamped within 5-10 s

Neonatal mortality, length of hospital stay

 27

Backes 2016

USA

Inclusion: singleton, preterm (22.5 – 27.6 weeks)

Exclusion: placental abruption, placental previa, multiple gestations, chromosomal abnormalities (including trisomy 21), known major congenital malformations, attending obstetrician refusal to participate

40

(DCC: 18; Control 22)

Cord was clamped between 30-45 s

Cord was clamped within 10 s

Neonatal mortality, length of hospital stay

 28

Berg 2021

Nepal

Inclusion: singleton, late preterm and term (34 – 41 weeks)

Exclusion: clinical history of hypertension, infection, diabetes, any chronic medical condition

347

(DCC: 179; Control: 168)

Cord was clamped at 180 s

Cord was clamped at < 60 s

Neurodevelopmental outcomes at 3 years (Ages and Stages Questionnaire -3)

 29

Cavallin 2019

Italy

Inclusion: singleton, elective caesarean section, term (> 39 weeks)

Exclusion: multiple gestations, major congenital malformations and/or chromosomic abnormalities, intrauterine growth restriction and/or fetal hydrops, cord abnormalities (i.e., a length < 20 cm, funicular prolapse, or funicular knots)

80 (DCC: 40; Control: 40)

Cord was clamped > 60 s

Cord was clamped within 10 s

Glucose concentration (at birth)

 30

Celikel 2022

Turkey

Inclusion: singleton, late term, term (36–42 weeks)

Exclusion: chronic systemic disease, endocrine or metabolic disease during pregnancy, chronic drug or multivitamin use, fetal anomalies, multiple pregnancy, infants with suspected sepsis, anomalies, fetal distress, requiring postnatal resuscitation

60

(DCC: 28; Control (32)

Cord clamping was done at 60 s

Cord clamping was done within 10 s

Admission to NICU

 31

Cernadas 2006

Argentina

Inclusion: singleton, term (> 37 weeks)

Exclusion: clinical disease (diabetes, preeclampsia, hypertension), any other complications; congenital malformations or intrauterine growth restriction (estimated fetal weight < 10th percentile)

254

(DCC: 1 min: 83; 3 min: 83; Control: 88)

Two delayed clamping groups, 60 s (45-75 s) and 3 min (> 150 s)

Cord was clamped within 15-20 s

Admission to NICU, length of hospital stay

 32

Chen 2018

China

Inclusion: singleton, term (37.0 – 41.6 weeks), birth weight 2500-400 g, vaginal delivery

Exclusion: mothers refusal; congenital fetal anomalies; Apgar < 6 at 1 min, requirement for resuscitation and oxygen therapy, severe IUGR (< 3%), mothers who received cortisone, anticonvulsants, antidepressants, thyroid hormone, or insulin

720

(DCC: 90 in each group; Control: 90)

The cord was clamped at 30 s, 60 s, 90 s, 120 s and 150 s

Cord was clamped at < 15 s (11.8 ± 2.5 s)

Admission to NICU

 33

Chopra 2018

India

Inclusion: low birth weight (< 25000 g) and late preterm (> 35 weeks)

Exclusion: placental abruption or previa, congenital malformations, Rh isoimmunised, multiple pregnancies. Post randomization exclusion criteria: infants born at 10th centile, needing resuscitation, infant birth weight ≥ 10th percentile

113

(DCC: 55; Control: 58)

Cord was clamped > 60 s

Cord was clamped immediately

Incidence of hypoglycaemia (undefined), neonatal mortality

 34

Das 2018

India

Inclusion: preterm (30.0–33.6 weeks)

Exclusion: multiple pregnancies, major congenital malformation, hydrops fetalis

At 40 weeks = 390

(Intervention:193, Control: 197)

At 9–12 months = 349 (Intervention: 171, Control: 178)

At 24–30 months = 323

(Intervention: 158, Control: 165)

Cord was clamped at 60 s

Cord was clamped within 10 s

Neurodevelopmental outcomes at 40 weeks post-menstrual age (Amiel-Tison) and 9–12 months corrected age (Denver II) and 24–30 months chronological age (Developmental Assessment Scale for Indian Infants)

 35

Datta 2017

India

Inclusion: singleton, preterm (34 – 36.6 weeks)

Exclusion: gross congenital anomaly, hydrops, Rhesus negative pregnancy

Baseline: 117

FU: 112

(DCC: Baseline: 58, FU: 54; Control: Baseline:59, FU: 58)

Cord was clamped between 30-60 s

Cord was clamped within 20 s

Neurodevelopmental outcomes at day 1- and 37-weeks CA (Neurobehavioral Assessment of Preterm Infant: motor development score)

 36

De Angelis 2022

Italy

Inclusion: singleton, vaginal delivery, term (37–41 weeks)

Exclusion: multiple pregnancies, preterm delivery, induced labour, operative delivery, maternal hypertension, abnormal placentation, maternal bleeding disorders, planned cord blood banking

122

(DCC: 62; Control: 60)

Cord was clamped < 60 s after birth, or when pulsation stopped

Cord was clamped within 15 s

Neonatal mortality, admission to NICU

 37

De Bernardo 2020

Italy

Inclusion: elective caesarean section, term (37–42 weeks), birth weight normal for gestational age

Exclusion: pathologies, toxicomaniac, those who smoked or took drugs during pregnancy; admitted to NICU or needing resuscitation, new-borns that showed hypoxic-ischemic events: detachment of placenta, prolapse of the funiculus, uterine rupture, shoulder dystocia, premature rupture of fetal membranes, placenta previa, maternal collapse, embolism amniotic, maternal cardiac arrest, monochorionic twins, fetal hydrops, umbilical cord damaged, isoimmunization Rh, respiratory, malformative diseases

132

(DCC: 66; Control: 66)

Cord was clamped at 60 s

Cord was clamped immediately after birth

Glucose concentration (2 h after birth)

 38

Digal 2021

India

Inclusion: singleton, IUGR, fetal weight < 10th percentile, preterm (≥ 28 weeks)

Exclusion: hemodynamic instability, placenta previa/abruptio placentae, multiple gestation, Rh-negative blood group, major congenital malformation, fetal hydrops, requiring resuscitation at birth; GA < 28 weeks

110 (DCC: 55; Control: 55)

Cord was clamped after 60 s

Cord was clamped within 30 s

Admission to NICU, length of hospital stay

 39/40

Duley 2017 /

Armstrong-Buisseret 2019

UK

Inclusion: preterm (< 32 weeks)

Exclusion: monochorionic twins; triplets or higher-order multiple pregnancy, major congenital malformation

270 (DCC: Baseline: 135; FU: 115; Control: Baseline: 135; FU:103)

Cord was clamped at ≥ 120 s

Cord was clamped within 20 s

Breastfeeding at discharge (undefined), neonatal mortality, length of hospital stay, neurodevelopmental outcomes at 2 years CA (Bayley Scales of Infant and Toddler development -III or Ages and Stages Questionnaire-3)

 41

Feitosa 2021

Brazil

Inclusion: singleton, term (37–42 weeks), vaginal delivery

Exclusion: High risk pregnancies, forceps delivery, resuscitation of neonate

580

(DCC: 278; Control: 282)

Cord clamping was done at 8 min (5 – 12.3 min), the umbilical cord was gently palpated every 30 s until pulsation stopped, allowing spontaneous drainage of blood from the placenta to the newborn

Cord remained intact and clamped at 180 s

Breastfeeding at discharge (exclusive), admission to NICU, length of hospital stay

 42

Hemmati 2020

Iran

Inclusion: preterm (26 – 34 weeks)

Exclusion: parent or clinician refusal, severe congenital anomalies, need for resuscitation, presence of placental abruption, placenta previa, clamping of the cord before or after the specified reference time intervals

148

(DCC: 69; Control: 79)

Cord was clamped between 30- 45 s

Cord was clamped after 10-15 s

Neonatal mortality, length of hospital stay

 43

Hofmeyer 1988

South Africa

Inclusion: singleton, preterm (35 weeks)

38

(DCC: 24; Control: 14)

Cord was clamped 60 s after birth

Cord was clamped immediately

Neonatal mortality

 44

Hofmeye, 1993

South Africa

Inclusion: low birth weight (< 2000 g)

86

(DCC: 40; Control: 46)

Cord was clamped 60-120 s after birth

Cord was clamped immediately

Neonatal mortality

 45

Jomjak 2021

Thailand

Inclusion: singleton, moderate – late preterm (32–36.6 weeks)

Exclusion: major severe congenital anomalies, chromosomal abnormalities, multifetal gestations, maternal coagulopathy, maternal anaemia, placenta previa, placenta abruption, fetal non-reassuring, fetal distress, non-vigorous neonate, denied participation

110

(DCC: 55, Control: 55)

Cord was clamped within 60 s

Cord was clamped within 5 s

Neonatal mortality, admission to NICU, length of hospital stay

 46

Korkut 2019

Turkey

Inclusion: singleton, maternal diabetes (any), term (≥ 37 weeks)

Exclusion: hydrops fetalis, major congenital anomaly, congenital infection, multiple gestation, no informed consent, any neonates whose birth was not attended by one of the researchers

80 (DCC: 40; Control: 40)

Cord was clamped at ≥ 60 s

Cord was clamped immediately after birth

Incidence of hypoglycaemia (defined as blood glucose levels of < 2.2 mmol/L in the first 4 h and < 2.5 mmol/L 3–24 h postnatally), severity of hypoglycaemia (severe hypoglycaemia defined as defined as blood glucose levels of < 1.4 mmol/L in the first 4 h and < 1.9 mmol/L 3–24 h postnatally), receipt of treatment for hypoglycaemia, admission to NICU

 46

Krishnan 2015

India

Inclusion: singleton, vaginal delivery, term (> 37 weeks)

Exclusion: pre-existing medical complications (heart disease, renal failure, other chronic illnesses); on any one of the following drugs (anticonvulsants, antidepressants, thyroid hormone, insulin, chemotherapy, or cortisone); infants anticipated to require resuscitation; major congenital anomalies; infants fed formula before obtaining ferritin levels at 6 weeks of age

76

(DCC: 37; Control: 39)

Cord was clamped 180 s

Cord was clamped 10 s after birth

Length of hospital stay

 48

Kugelman 2007

Israel

Inclusion: preterm (24 – 34.6/7 weeks)

Exclusion: parents refused consent; vaginal bleeding due to placenta previa or abruption or placental tear; major anomaly; severe intrauterine growth restriction (IUGR; < 3%); maternal gestational diabetes treated with insulin; suspected twins, twin transfusion syndrome or discordant twins; and maternal drug abuse

65

(DCC: 30; Control: 35)

Cord was clamped 30-45 s

Cord was clamped < 10 s

Neonatal mortality, glucose concentration (undefined timing—in delivery room), length of hospital stay

 49

Mercer 2022

USA

Inclusion: singleton, term (37 – 41.6 weeks)

Exclusion: medical or obstetrical complications (hypertension, pre-eclampsia, diabetes, smoking, substance abuse and suspected intrauterine growth restriction), infants with evidence of intrauterine growth restriction, serious congenital anomalies

41 (DCC: 21; Control: 20)

Cord was clamped at ≥ 5 min (if cord couldn’t be clamped it was milked 5 times before clamping)

Cord was clamped at < 20 s

Neurodevelopmental outcomes at 12 months (Mullen Scale of Early Learning; Brief Infant Toddler Social Emotional Assessment)

 50

Mercer 2018

USA

Inclusion: singleton, term (37 – 41.6 weeks)

Exclusion: medical or obstetrical complications (hypertension, pre-eclampsia, diabetes, smoking, substance abuse and suspected intrauterine growth restriction)

56

(DCC: 31; Control: 25)

Cord was clamped at > 5 min. If unable to delay the clamp, cord was milked 5 times before clamping. Clamp time was 172 s ± 188 s)

Cord was clamped < 20 s (28 s ± 7.6 s)

Neurodevelopmental outcomes at 4 months (Mullen Scales of Early learning)

 51

Mercer 2017

USA

Inclusion: singleton, term (37 – 41.7 weeks)

Exclusion: evidence of medical or obstetrical complications (hypertension, pre-eclampsia, diabetes, smoking, substance abuse and suspected intrauterine growth restriction), infants with evidence of intrauterine growth restriction, serious congenital anomalies

73

(DCC: 37; Control: 36)

Cord was clamped at > 5 min. If unable to delay the clamp, cord was milked 5 times before clamping

Cord was clamped < 20 s (23.1 s ± 5.9 s)

Breastfeeding at discharge (undefined)

 52

Mercer 2010

USA

Inclusion: preterm (24 – 31.6 weeks)

Exclusion: obstetrician’s refusal to participate, major congenital anomalies, multiple gestations, intent to withhold care, severe maternal illnesses, placenta abruption or previa

58

(DCC: 29; Control: 29)

Cord was clamped 30-45 s

Cord was clamped < 10 s

Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler development -II) at 7.3 months CA

 53

Mercer 2003

USA

Inclusion: singleton, preterm (24–31.6/7 weeks)

Exclusion: obstetrician or parents refused consent, intent to withhold or withdraw care, placenta previa or abruption, maternal bleeding, major anomaly

32

(DCC: 16, Control: 16)

Cord was clamped 30-45 s

Cord was clamped 5-10 s

Incidence of hypoglycaemia (defined as blood glucose < 2.2 mmol/L in first 4 h postnatally), glucose concentration (within the first 12 h), length of hospital stay

 54

Nouraie 2019

Iran

Inclusion: term (> 37 weeks)

Exclusion: maternal complications (diabetes, cardiovascular, renal-pulmonary diseases, preeclampsia, placental abruption and polyhydramnios), mothers most recent delivery had not required the use of forceps or vacuum extractors and was not accompanied with complications such as haemorrhage, dystocia or prolonged labour, no history of known developmental (genetic) disorders or congenital anomalies in either parent families, preterm birth, Apgar score of ≥ 7, birth weight > 2.5 kg

400 (DCC: 200; Control: 200)

Cord was clamped between 90-120 s

Cord was clamped < 60 s

Neurodevelopmental outcomes at 4 months (Ages and Stages Questionnaire)

 55

Oxford Midwives Research Group. 1991

UK

Inclusion: vaginal delivery, singleton, term (> 37 weeks)

Exclusion: receiving medication other than iron and vitamin supplements; women whose baby was to be adopted; parents who had a specific preference for early or late cord clamping; babies who showed signs of stress in utero

552

(DCC: 296; Control: 256)

Cord was clamped 180 s after birth, or when pulsation stopped

Cord was clamped “as soon as possible” after birth

Breastfeeding at discharge (undefined)

 56

Purisch 2019

USA

Inclusion: singleton, elective caesarean section, term (≥ 37.0 weeks)

Exclusion: placenta previa, placenta abruption, prenatally diagnosed fetal anomalies, fetal anaemia, fetal growth restriction, preeclampsia, significant maternal anaemia, bleeding disorders, planned cord blood banking, refusal of blood products, women with caesarean deliveries scheduled on weekends or postponed to evening hours

113 (DCC: 57; Control: 56)

Cord was clamped at 60 s (63 s, IQR 61-65 s)

Cord was clamped within 15 s (6 s, IQR 5-8 s)

Admission to NICU

 57

Rana 2019

Nepal

Inclusion: vaginal delivery, term (> 37 weeks)

Exclusions: any complications

540

(DCC: 270; Control: 270)

Cord was clamped at ≥ 180 s

Cord was clamped at ≤ 60 s

Neurodevelopmental outcomes (Ages and Stages Questionnare-3) at 12 months CA

 58

Rana 2018

India

Inclusion: preterm (< 34 weeks)

Exclusion: known congenital malformations, serious maternal illnesses (severe preeclampsia or eclampsia, uncompensated heart disease, any abnormal bleeding before cord clamping), twins or triplets, and babies requiring immediate resuscitation at birth

100

(DCC: 50; Control: 50)

Cord was clamped after 120 s

Cord was clamped < 30 s

Length of hospital stay

 59

Ranjit 2015

India

Inclusion: preterm (30 – 36.6 weeks)

Exclusion: Rhesus negative blood group, monoamniotic/monochorionic twins, babies who did not receive the intervention due to need for resuscitation at birth

94

(DCC: 44; Control: 50)

Cord was clamped > 120 s

Cord was clamped immediately

Incidence of hypoglycaemia (undefined), neonatal mortality

 60

Rashwan 2022

Egypt

Inclusion: singleton, assigned caesarean section, late term – term (36 – 38.6 weeks)

Exclusion: intrapartum surgical complications such as uterine artery injury or lower segment extension, intrauterine fetal demise, medical disorders (anaemia, diabetes mellitus, abnormal placentation, placenta abruption, liquor abnormalities, or anomalous foetuses)

62 (DCC: 31; Control: 31)

Cord was clamped at 60 s

Cord was clamped within 15 s

Admission to NICU

 61

Robledo 2022

Australia

Inclusion: preterm (< 30 weeks)

Exclusion: fetal haemolytic disease, hydrops fetalis, twin transfusion, genetic syndromes, malformations

1419

(DCC: 709; Control: 710)

Cord was clamped at ≥ 60 s

Cord was clamped within 10 s

Neurodevelopmental outcomes at 2 years CA (Major disability as diagnosed by CP, vision loss, deafness, language problems; Ages and Stages Questionnaire-3)

 62

Ruangkit 2019

Thailand

Inclusion: multiple gestations, preterm (28–36 weeks)

Exclusion: diagnosed major congenital anomaly, twin-to-twin transfusion syndrome, twin anemic-polycythemic sequence, discordant twins (a weight difference of > 20%), neonatal mortality, hydrops, antepartum or intrapartum haemorrhage, when the medical care provider declined performing DCC

101 (DCC:51; Control: 50)

Cord was clamped at 30-60 s

Cord was clamped immediately (< 5 s)

Neonatal mortality, glucose concentration (on admission), length of hospital stay

 63

Shao 2022

China

Inclusion: gestational diabetes, pre-diabetes and non-diabetic pregnancies, term (> 37 weeks)

Exclusion: mothers with other pregnancy complications (hypertension disorders, intrahepatic cholestasis of pregnancy, maternal fever, multiple

pregnancy, preterm labour, post-term pregnancy, emergency caesarean section, abnormal fetal presentation), birth weight < 2500 g, Apgar score of < 7, neonatal malformation, suspicious fetal distress, neonatal resuscitation, failed cord blood collection failed, missed blood gas parameters

441

(DCC: GDM:73, non-GDM: 107;

Control: GDM:87, non-GDM:101)

Cord was clamped > 30 s

Cord was clamped < 15 s

Glucose concentration (within 15 min)

 64

Shinohara 2021

Japan

Inclusion: singleton, vaginal delivery, term (> 37 weeks)

Exclusion: maternal complications, fetal complications, emergency caesarean section, transferred to another hospital, not literate in Japanese, unable to return in 4 months

138 (DCC:68; Control: 70)

Cord was clamped at > 60 s or when pulsation stopped

Cord was clamped within 15 s

Breastfeeding at discharge (exclusive), neonatal mortality, ddmission to NICU

 65

Soliman 2022

Egypt

Inclusion: term (> 37 weeks), elective caesarean

Exclusion: history of inutero fetal distress, active resuscitation, twin or multiple gestation deliveries; major congenital anomalies, intrauterine growth restriction, perinatal asphyxia, perinatal hypoxic, ischemic event, Apgar score < 5 at 5 min, fetal umbilical artery pH < 7.0, and/or base deficit ≥ 16 mmol/L, presence of multisystem organ failure

68 (DCC:34; Control: 34)

Cord clamping was done at 120 s

Cord was clamped at 30 s

Glucose concentration (24 h after birth)

 66

Songthamwat 2020

Thailand

Inclusion: singleton, vaginal delivery, term (37–41 weeks)

Exclusion: severe medical complication (heart disease, chronic hypertension, or renal disease), fetal anomaly, fetal growth restriction, birth asphyxia, heavy bleeding immediately after birth, refusal to participate in the study

230

(DCC: 1 min: 76, 2 min: 77; Control: 77)

Two delayed clamping groups, 60 s and 120 s

Cord was clamped at 30 s

Admission to NICU

 67

Songthamwat 2020b

Thailand

Inclusion: singleton, elective caesarean section, term (< 37 weeks)

Exclusion: severe medical complication, fetal anomaly, fetal growth restriction, heavy bleeding immediately after birth, refusal to participate in this study, birth asphyxia, non-vigorous infant

159

(DCC: 80; Control: 79)

Cord was clamped at 60 s

Cord was clamped < 30 s

Admission to NICU

 68

Tarnow-Mordi 2017

Australia

Inclusion: preterm (< 30 weeks)

Exclusion: fetal haemolytic disease, hydrops fetalis, twin transfusion, genetic syndromes, malformations

1566

(DCC: 784; Control: 782)

Cord was clamped at ≥ 60 s

Cord was clamped ≤ 10 s

Neonatal mortality

 69

Ultee 2007

The Netherlands

Inclusion: vaginal delivery, preterm (34.0 – 36.6 weeks)

Exclusion: maternal overt diabetes or gestational diabetes, pregnancy-induced hypertension

37

(DCC: 18; Control: 19)

Cord was clamped within 180 s

Cord was clamped within 30 s (13.4 ± 5.6 s)

Incidence of hypoglycaemia (defined as < 2.0 mmol/L), glucose concentration (3 h after birth)

 70

Vural 2018

Turkey

Inclusion: macrosomia (4000-4500 g), term (37 – 42 weeks)

Exclusion: birth weight < 4000 g, need for resuscitation, < 37w or > 42w gestation, congenital heart disease, congenital malformations

51 (DCC: 25; Control: 26)

Cord clamping at 60 s after birth

Cord was clamped at 15 s after birth

Length of hospital stay

 71

Yunis 2021

Egypt

Inclusion: preterm (< 34 weeks), mothers with antenatal diagnosis of placental insufficiency

Exclusion: congenital anomaly, chromosomal anomaly, major resuscitation where delay of resuscitation was not possible

90

(DCC: 60; Control: 30)

Cord was clamped at 60 s

Cord was clamped within 10 s

Incidence of hypoglycaemia (defined by pre-feeding blood glucose level < 2.5 mmol/L), neonatal mortality, length of hospital stay

  1. Abbreviations: UCM Umbilical cord milking, DCM Delayed cord milking, S seconds, NICU Neonatal intensive care unit, CA Corrected age, IUGR Intrauterine growth restriction, GA Gestational age, CP Cerebral palsy