Indian J Pediatr DOI 10.1007/s12098-013-1329-8
ORIGINAL ARTICLE
Effect of Early versus Delayed Cord Clamping on Hematological Status of Preterm Infants at 6 wk of Age Thomas Ranjit & Saudamini Nesargi & P. N. Suman Rao & Jagdish Prasad Sahoo & C. Ashok & B. S. Chandrakala & Swarnarekha Bhat
Received: 22 April 2013 / Accepted: 26 December 2013 # Dr. K C Chaudhuri Foundation 2014
Abstract Objective To compare the effect of early cord clamping (ECC) vs. delayed cord clamping (DCC) on hematocrit and serum ferritin at 6 wk of life in preterm infants. Methods This randomized controlled trial was conducted in the delivery room and neonatal intensive care unit of a tertiary hospital. One hundred preterm infants born between 30 0/7 and 36 6/7 wk were randomized to either early or delayed cord clamping groups. Parental informed consent was obtained prior to the delivery. In the ECC group, the cord was clamped immediately after the delivery of the baby and in the DCC group; the cord was clamped beyond 2 min after the baby was delivered. Hematocrit and serum ferritin at 6 wk of life were the primary outcomes. Incidence of anemia, polycythemia and significant jaundice were the main secondary outcomes. Results The mean hematocrit (27.3±3.8 % vs. 31.8±3.5 %, p value 0.00) and the mean serum ferritin (136.9±83.8 ng/mL vs. 178.9±92.8 ng/mL, p value 0.037) at 6 wk of age were significantly higher in the infants randomized to DCC group. The hematocrit on day 1 was also significantly higher in the DCC group (50.8 ±5.2 % vs. 58.5 ±5.1 %, p value 0.00). The DCC group required significantly longer duration of phototherapy (55.3±40.0 h vs. 36.7±32.6 h, p value 0.016) and had a trend towards higher risk of polycythemia. Conclusions Delaying the cord clamping by 2 min, significantly improves the hematocrit value at birth and this beneficial effect continues till at least 2nd mo of life.
Keywords Cord clamping . Ferritin . Hematocrit . Anemia . Preterm
Introduction Iron deficiency is the commonest nutritional disorder in the world [1]. In India, almost 70 % of infants between 6 and 59 mo of age are anemic [2]. Delayed cord clamping has been suggested as a possible strategy for reducing anemia amongst young infants as they are largely dependent on the supply of iron present at birth for hemoglobin production and growth during the first 6 mo of life. In early cord clamping, a potential source of iron is wasted making these children more prone for iron deficiency anemia. Neonatal Resuscitation Guidelines of 2010 recommend delaying umbilical cord clamping for at least 1 min for newborn infants not requiring resuscitation [3]. Despite recent systematic reviews and meta-analysis suggesting that delayed cord clamping is beneficial, immediate cord clamping is still the standard practice among obstetricians especially in preterm infants. There have been Indian trials to look at the benefits of delayed cord clamping in term neonates [4, 5]. This study was conducted in preterm neonates to add to the existing evidence on the benefits and the safety profile of delayed cord clamping in preterm neonates.
Material and Methods T. Ranjit : S. Nesargi : P. N. S. Rao : J. P. Sahoo : C. Ashok : B. S. Chandrakala : S. Bhat Department of Neonatology, St. John’s Medical College & Hospital, Bangalore, Karnataka, India T. Ranjit (*) Department of Neonatology, CIMAR COCHIN Hospital, Cheranallore, Edapally, Kochi 682034, India e-mail: [email protected]
This randomized controlled trial was conducted in a tertiary care hospital in South India from May 2010 through November 2010. The study was approved by the institutional ethical review board. All neonates born between 30 0/7 and 36 6/7 wk of gestation were included in the study. Gestational age assessment was based on first trimester ultrasonography or mother’s last menstrual period if it was reliable. An informed
Indian J Pediatr
written consent was taken, by the principal investigator, from either parent on admission to the labor room. Mothers with Rhesus negative blood group and monoamniotic – monochorionic twins were excluded. Babies who were randomized to delayed cord clamping group, but did not receive the intervention due to need for resuscitation at birth, were excluded from the analysis. The eligible babies were randomized into 2 groups – early cord clamping (ECC) group and delayed cord clamping (DCC) group based on computer generated random numbers. Allocation concealment was achieved by sequentially numbered opaque sealed envelopes containing the codes for intervention. The obstetrician conducting the delivery was informed the group allocation prior to the delivery. In the ECC group, the cord was clamped immediately after delivery of the infant, the standard practice at authors’ institution. In the DCC group, the cord was clamped beyond 2 min of the delivery of the infant. Until the cord was clamped, the baby was placed covered on the mother’s abdomen in case of vaginal deliveries or on the mother’s thigh in case of Cesarean deliveries. The investigator (principal investigator/co-investigator) was present for all the deliveries included in the study. The need for resuscitation was assessed at birth, and in babies needing resuscitation at birth, immediate cord clamping was practiced irrespective of group allocation. Hematocrit and serum ferritin levels at 6 wk of age were the primary outcomes. Anemia at 6 wk was defined as hematocrit 35 wk [6] and phototherapy guidelines for very low birth weight infants [7]. Anemia and polycythemia on day 1 were defined as hematocrit 65 % respectively. The maternal and perinatal details relevant for the study were collected prospectively in pre-designed case reporting form at birth. The maternal details included age, parity, hemoglobin, antenatal complications and mode of delivery. Gestational age, birth weight and APGAR scores at 1 and 5 min were also noted. The hematocrit was estimated in all infants between 12 and 24 h of life. Treatment of other neonatal illness was as per standard unit protocols. In all stable preterm infants 0.05 except maternal hemoglobin (p=0.004) +
mean±SD
44 completed initial analysis
41 completed follow-up analysis
blood in the placenta to the infant at the time of birth. This placental transfusion can provide the infant with an additional 30 % blood volume [9]. The authors found DCC quite safe. Although there was a trend towards polycythemia in the DCC group, the difference was not significant. There was however a significantly longer requirement of phototherapy in the DCC group, probably due to the higher hemoglobin and bilirubin pool in these babies, however the incidence of significant jaundice was not different. The authors did not find a significant effect of the intervention on neonatal mortality or other neonatal morbidities viz. PDA, RDS, NEC, TTNB, IVH, sepsis, hypoglycemia, apnea and shock. This could be due to the low occurrence of the above morbidities in both the groups. Several well designed randomized controlled trials in term infants on DCC have shown benefits of higher hemoglobin levels [4, 8–11], lesser anemia [9] and better iron stores [10, 12] in the early neonatal period and extending to early infancy [4, 8, 10]. Potential disadvantages of delayed cord clamping in term babies are polycythemia [8, 11], jaundice [13] and increased requirement of phototherapy [13]. Two major metaanalysis had concluded that DCC in term infants improves the hematological status of the babies in early infancy [14, 15] with a minor risk of polycythemia [14] and jaundice requiring phototherapy [15]. Although several studies on DCC have been conducted in preterm neonates, their results have been inconsistent. Immediate cord clamping is still the standard practice in preterm infants. Preterm babies, when clamped late, have been shown to have higher hemoglobin [16–21], better iron stores [16], lesser transfusion requirement [18, 19, 22], higher blood pressure [17, 19, 23], better cerebral oxygenation [24], lower rates of IVH [20, 25, 26] lesser ventilation and surfactant requirement [17], lower rates of late onset sepsis [20] and lesser motor disability [27]. Studies have failed to demonstrate the effects of timing of cord clamping on development of PDA [19, 21],
Indian J Pediatr Table 2 Neonatal morbidities and hematological parameters ECC Group (n=50)
DCC Group (n=44)
Difference in mean/RR (95 % CI)
Hct 1 (%) *$ Hct 2 (%)*#$ Ferritin (ng/mL)*# $ Duration of phototherapy (hours) *$ Mean peak bilirubin$ Anemia on day 1*€ Polycythemia€ Patent ductus arteriosus€ Significant jaundice€ Respiratory distress syndrome€ Necrotizing enterocolitis€ Transient tachypnea of newborn€ Sepsis€ Intraventricular hemorrhage€ Hypoglycemia€ Apnea€ Shock€
50.8±5.2 (37.5–63.8) 27.3±3.8 (18.6–34.4) 136.9±83.8 (30.2–356.2) 36.7±32.6 12.4±3.9 6 (12) 0 3 (6) 37 (74) 8 (16) 2 (4) 1 (2) 13 (26) 1 (1) 11 (22) 5 (10) 3 (6)
58.5±5.1 (46.5–70.8) 31.8±3.5 (21.6–37.7) 178.9±92.8 (86.0–495.7) 55.3±40.0 13.1±3.2 0 3 (7) 3 (7) 37 (84) 5 (11) 5 (11) 5 (11) 10 (23) 0 8 (18) 2 (4.5) 4 (9)
7.2 (5–9.56) 4.84 (3.2–6.4) 39.6 (0.83–78.5) 15.5 (1.03–32) −0.64 (−2.37−1.08) 0.087 (0.005–1.50) 7.93 (0.42–149.46) 1.13 (0.24–5.34) 1.07 (0.76–1.51) 0.581 (0.19–1.79) 2.81 (0.58–13.91) 5.68 (0.69–46.7) 0.8 (0.42–1.79) 0.37 (0.02–9.04) 0.82 (0.36–1.86) 0.45 (0.09–2.27) 1.5 (0.35–6.4)
Hypoxic ischemic encephalopathy€ Acute kidney injury€ Death€
2 (4) 2 (4) 5 (10)
1 (2) 0 0
0.56 (0.05–6.03) 0.27 (0.01–6) 0.103 (0.006–1.81)
* p value
ORIGINAL ARTICLE
Effect of Early versus Delayed Cord Clamping on Hematological Status of Preterm Infants at 6 wk of Age Thomas Ranjit & Saudamini Nesargi & P. N. Suman Rao & Jagdish Prasad Sahoo & C. Ashok & B. S. Chandrakala & Swarnarekha Bhat
Received: 22 April 2013 / Accepted: 26 December 2013 # Dr. K C Chaudhuri Foundation 2014
Abstract Objective To compare the effect of early cord clamping (ECC) vs. delayed cord clamping (DCC) on hematocrit and serum ferritin at 6 wk of life in preterm infants. Methods This randomized controlled trial was conducted in the delivery room and neonatal intensive care unit of a tertiary hospital. One hundred preterm infants born between 30 0/7 and 36 6/7 wk were randomized to either early or delayed cord clamping groups. Parental informed consent was obtained prior to the delivery. In the ECC group, the cord was clamped immediately after the delivery of the baby and in the DCC group; the cord was clamped beyond 2 min after the baby was delivered. Hematocrit and serum ferritin at 6 wk of life were the primary outcomes. Incidence of anemia, polycythemia and significant jaundice were the main secondary outcomes. Results The mean hematocrit (27.3±3.8 % vs. 31.8±3.5 %, p value 0.00) and the mean serum ferritin (136.9±83.8 ng/mL vs. 178.9±92.8 ng/mL, p value 0.037) at 6 wk of age were significantly higher in the infants randomized to DCC group. The hematocrit on day 1 was also significantly higher in the DCC group (50.8 ±5.2 % vs. 58.5 ±5.1 %, p value 0.00). The DCC group required significantly longer duration of phototherapy (55.3±40.0 h vs. 36.7±32.6 h, p value 0.016) and had a trend towards higher risk of polycythemia. Conclusions Delaying the cord clamping by 2 min, significantly improves the hematocrit value at birth and this beneficial effect continues till at least 2nd mo of life.
Keywords Cord clamping . Ferritin . Hematocrit . Anemia . Preterm
Introduction Iron deficiency is the commonest nutritional disorder in the world [1]. In India, almost 70 % of infants between 6 and 59 mo of age are anemic [2]. Delayed cord clamping has been suggested as a possible strategy for reducing anemia amongst young infants as they are largely dependent on the supply of iron present at birth for hemoglobin production and growth during the first 6 mo of life. In early cord clamping, a potential source of iron is wasted making these children more prone for iron deficiency anemia. Neonatal Resuscitation Guidelines of 2010 recommend delaying umbilical cord clamping for at least 1 min for newborn infants not requiring resuscitation [3]. Despite recent systematic reviews and meta-analysis suggesting that delayed cord clamping is beneficial, immediate cord clamping is still the standard practice among obstetricians especially in preterm infants. There have been Indian trials to look at the benefits of delayed cord clamping in term neonates [4, 5]. This study was conducted in preterm neonates to add to the existing evidence on the benefits and the safety profile of delayed cord clamping in preterm neonates.
Material and Methods T. Ranjit : S. Nesargi : P. N. S. Rao : J. P. Sahoo : C. Ashok : B. S. Chandrakala : S. Bhat Department of Neonatology, St. John’s Medical College & Hospital, Bangalore, Karnataka, India T. Ranjit (*) Department of Neonatology, CIMAR COCHIN Hospital, Cheranallore, Edapally, Kochi 682034, India e-mail: [email protected]
This randomized controlled trial was conducted in a tertiary care hospital in South India from May 2010 through November 2010. The study was approved by the institutional ethical review board. All neonates born between 30 0/7 and 36 6/7 wk of gestation were included in the study. Gestational age assessment was based on first trimester ultrasonography or mother’s last menstrual period if it was reliable. An informed
Indian J Pediatr
written consent was taken, by the principal investigator, from either parent on admission to the labor room. Mothers with Rhesus negative blood group and monoamniotic – monochorionic twins were excluded. Babies who were randomized to delayed cord clamping group, but did not receive the intervention due to need for resuscitation at birth, were excluded from the analysis. The eligible babies were randomized into 2 groups – early cord clamping (ECC) group and delayed cord clamping (DCC) group based on computer generated random numbers. Allocation concealment was achieved by sequentially numbered opaque sealed envelopes containing the codes for intervention. The obstetrician conducting the delivery was informed the group allocation prior to the delivery. In the ECC group, the cord was clamped immediately after delivery of the infant, the standard practice at authors’ institution. In the DCC group, the cord was clamped beyond 2 min of the delivery of the infant. Until the cord was clamped, the baby was placed covered on the mother’s abdomen in case of vaginal deliveries or on the mother’s thigh in case of Cesarean deliveries. The investigator (principal investigator/co-investigator) was present for all the deliveries included in the study. The need for resuscitation was assessed at birth, and in babies needing resuscitation at birth, immediate cord clamping was practiced irrespective of group allocation. Hematocrit and serum ferritin levels at 6 wk of age were the primary outcomes. Anemia at 6 wk was defined as hematocrit 35 wk [6] and phototherapy guidelines for very low birth weight infants [7]. Anemia and polycythemia on day 1 were defined as hematocrit 65 % respectively. The maternal and perinatal details relevant for the study were collected prospectively in pre-designed case reporting form at birth. The maternal details included age, parity, hemoglobin, antenatal complications and mode of delivery. Gestational age, birth weight and APGAR scores at 1 and 5 min were also noted. The hematocrit was estimated in all infants between 12 and 24 h of life. Treatment of other neonatal illness was as per standard unit protocols. In all stable preterm infants 0.05 except maternal hemoglobin (p=0.004) +
mean±SD
44 completed initial analysis
41 completed follow-up analysis
blood in the placenta to the infant at the time of birth. This placental transfusion can provide the infant with an additional 30 % blood volume [9]. The authors found DCC quite safe. Although there was a trend towards polycythemia in the DCC group, the difference was not significant. There was however a significantly longer requirement of phototherapy in the DCC group, probably due to the higher hemoglobin and bilirubin pool in these babies, however the incidence of significant jaundice was not different. The authors did not find a significant effect of the intervention on neonatal mortality or other neonatal morbidities viz. PDA, RDS, NEC, TTNB, IVH, sepsis, hypoglycemia, apnea and shock. This could be due to the low occurrence of the above morbidities in both the groups. Several well designed randomized controlled trials in term infants on DCC have shown benefits of higher hemoglobin levels [4, 8–11], lesser anemia [9] and better iron stores [10, 12] in the early neonatal period and extending to early infancy [4, 8, 10]. Potential disadvantages of delayed cord clamping in term babies are polycythemia [8, 11], jaundice [13] and increased requirement of phototherapy [13]. Two major metaanalysis had concluded that DCC in term infants improves the hematological status of the babies in early infancy [14, 15] with a minor risk of polycythemia [14] and jaundice requiring phototherapy [15]. Although several studies on DCC have been conducted in preterm neonates, their results have been inconsistent. Immediate cord clamping is still the standard practice in preterm infants. Preterm babies, when clamped late, have been shown to have higher hemoglobin [16–21], better iron stores [16], lesser transfusion requirement [18, 19, 22], higher blood pressure [17, 19, 23], better cerebral oxygenation [24], lower rates of IVH [20, 25, 26] lesser ventilation and surfactant requirement [17], lower rates of late onset sepsis [20] and lesser motor disability [27]. Studies have failed to demonstrate the effects of timing of cord clamping on development of PDA [19, 21],
Indian J Pediatr Table 2 Neonatal morbidities and hematological parameters ECC Group (n=50)
DCC Group (n=44)
Difference in mean/RR (95 % CI)
Hct 1 (%) *$ Hct 2 (%)*#$ Ferritin (ng/mL)*# $ Duration of phototherapy (hours) *$ Mean peak bilirubin$ Anemia on day 1*€ Polycythemia€ Patent ductus arteriosus€ Significant jaundice€ Respiratory distress syndrome€ Necrotizing enterocolitis€ Transient tachypnea of newborn€ Sepsis€ Intraventricular hemorrhage€ Hypoglycemia€ Apnea€ Shock€
50.8±5.2 (37.5–63.8) 27.3±3.8 (18.6–34.4) 136.9±83.8 (30.2–356.2) 36.7±32.6 12.4±3.9 6 (12) 0 3 (6) 37 (74) 8 (16) 2 (4) 1 (2) 13 (26) 1 (1) 11 (22) 5 (10) 3 (6)
58.5±5.1 (46.5–70.8) 31.8±3.5 (21.6–37.7) 178.9±92.8 (86.0–495.7) 55.3±40.0 13.1±3.2 0 3 (7) 3 (7) 37 (84) 5 (11) 5 (11) 5 (11) 10 (23) 0 8 (18) 2 (4.5) 4 (9)
7.2 (5–9.56) 4.84 (3.2–6.4) 39.6 (0.83–78.5) 15.5 (1.03–32) −0.64 (−2.37−1.08) 0.087 (0.005–1.50) 7.93 (0.42–149.46) 1.13 (0.24–5.34) 1.07 (0.76–1.51) 0.581 (0.19–1.79) 2.81 (0.58–13.91) 5.68 (0.69–46.7) 0.8 (0.42–1.79) 0.37 (0.02–9.04) 0.82 (0.36–1.86) 0.45 (0.09–2.27) 1.5 (0.35–6.4)
Hypoxic ischemic encephalopathy€ Acute kidney injury€ Death€
2 (4) 2 (4) 5 (10)
1 (2) 0 0
0.56 (0.05–6.03) 0.27 (0.01–6) 0.103 (0.006–1.81)
* p value
