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ORIGINAL ARTICLE
Year : 2015  |  Volume : 4  |  Issue : 3  |  Page : 183-187

Should delayed cord clamping be the standard of care in term low risk deliveries? A randomized controlled trial from a medical college hospital in south India


1 Department of Pediatrics, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry, India
2 Department of Biostatistics, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry, India
3 Department of Obstetrics and Gynecology, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry, India

Date of Web Publication2-Jul-2015

Correspondence Address:
Lalitha Krishnan
Department of Pediatrics, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry - 605 014
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.159904

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  Abstract 

Objective: The objective was to compare the effects of early versus delayed cord clamping (ECC vs. DCC) on immediate neonatal adverse outcomes and delayed benefits. Methodology: Prospective randomized controlled trial in mother-infant pairs who were term, singleton with uneventful pregnancies and normal vaginal deliveries. Intervention: ECC done at 10 s after birth. DCC done at 180 s after complete delivery of the fetus. Results: A sample size of 86 mothers were included, but 10 infant blood samples were discarded because they were hemolyzed. Hence final analysis was done on 76 mother-infant pairs (ECC = 39; DCC = 37). Mean serum ferritin level was 299.7 ng/ml in the ECC group versus 399.9 ng/ml in the DCC group with no significant complications in either group. Multiple regression analysis confirmed a clear relationship between DCC and serum ferritin levels after accounting for the effect of secondary variables. Conclusion: DCC should become the standard of care in all low risk singleton pregnancies.

Keywords: Cord clamping, delayed, early, serum ferritin


How to cite this article:
Krishnan L, Kommu PP, Thomas BJ, Akila B, Daniel M. Should delayed cord clamping be the standard of care in term low risk deliveries? A randomized controlled trial from a medical college hospital in south India. J Clin Neonatol 2015;4:183-7

How to cite this URL:
Krishnan L, Kommu PP, Thomas BJ, Akila B, Daniel M. Should delayed cord clamping be the standard of care in term low risk deliveries? A randomized controlled trial from a medical college hospital in south India. J Clin Neonatol [serial online] 2015 [cited 2020 Aug 13];4:183-7. Available from: http://www.jcnonweb.com/text.asp?2015/4/3/183/159904


  Introduction Top


Iron deficiency anemia is a major public health problem in young children resulting in increased mortality and poor neurodevelopmental outcome. [1],[2] Preventing iron deficiency is thus of critical importance and delaying clamping of the umbilical cord could be an effective strategy to reduce anemia and improve child survival. The advocates of early cord clamping (ECC) argue that the excess blood could lead to respiratory distress and jaundice in the newborn and would interfere with the active management of the third stage of labor. Proponents of delayed cord clamping (DCC) on the other hand claim that this is the natural termination of a healthy pregnancy. Studies in the last decade of the 20 th century supported the fact that DCC could give the newly born infant much needed iron stores. [3] Over the next decade, a few studies were published examining the benefits of ECC versus DCC, including two meta-analyses. [4],[5],[6],[7] Others have shown increased risk of respiratory symptoms [8] and expiratory grunting in the late clamped normal neonate, [9] polycythemia, [10] hyperbilirubinemia, [11] and need for phototherapy. [6]

Very few studies have been published in Indian population and to our knowledge none from South India. [3],[12] We, therefore, undertook this randomized clinical trial to compare the effects of ECC versus DCC on immediate neonatal adverse outcomes like respiratory distress, polycythemia, hyperbilirubinemia, and delayed benefits like serum ferritin levels.


  Methodology Top


This was a prospective randomized controlled trial in mother-infant pairs with term, singleton, uneventful pregnancies and normal vaginal deliveries, carried out in a Tertiary Hospital in South India. The period of study was 12 months from April 2012 to March 2013.

Primary outcome was to compare serum ferritin levels at 6 weeks of age in newborns with ECC and DCC. Secondary outcomes were total bilirubin and hemoglobin (Hb) at 24 h of age, development of respiratory distress in the first 24 h, and jaundice requiring phototherapy.

Inclusion criteria

  • Maternal Hb >10 g/dl at admission for delivery
  • Term (37-41 completed weeks of gestation)
  • Singleton
  • Normal vaginal delivery with cephalic presentation.


Exclusion criteria

  • Preexisting 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
  • Infants born with major congenital anomalies
  • Infants fed formula before obtaining ferritin levels at 6 weeks of age.


Sample size

Sample size was calculated to detect a difference of 50 ng/ml in serum ferritin levels between the ECC and DCC groups with 80% power and 5% level of significance. This was 41 in each group. Assumptions made were mean serum ferritin levels in ECC group as 250 ng/ml and the mean serum ferritin levels in DCC group as 300 ng/ml with a standard deviation in serum ferritin levels of 70 ng/ml. There were 86 mother-infant pairs who fulfilled the enrolment criteria. They were randomized to either early (n = 43) or late clamping (n = 43) groups at the time of delivery by opening chits placed in an opaque envelope, containing the name of each group.

Intervention

Eligible mothers included in the study were informed about the nature of the study, randomization, DCC and ECC, its advantages and disadvantages, and follow-up. Signed consent was taken before the delivery. All deliveries were attended by the principal investigator. The study was approved by the Institutional Ethics Committee.

Early cord clamping

This is currently done at 10 s after birth in this hospital and the same procedure was retained for the study.

Delayed cord clamping

In these cases, the cord was clamped at 180 s after complete delivery of the fetus.

Infants of both groups were held 10 cm below the delivery bed, on a specially assigned trolley. The time from complete expulsion of the fetus till the first clamp was measured using a stopwatch by an assistant in DCC groups. 10 IU oxytocin was given to the mother immediately after cord clamping in both groups.

All babies were closely monitored till discharge. Data like respiratory rate at 6, 12, and 24 h of life were recorded for assessment of respiratory function. Jaundice was assessed clinically as per hospital policy. At discharge, mothers were advised to exclusively breastfeed the infants on demand till 6 months of age, and this was telephonically re-emphasized till 6 weeks of age.

Blood samples

Blood samples were collected at 24 h of life in a clotted tube for assessing total and direct bilirubin levels and in EDTA for Hb and hematocrit values. The samples for baby serum ferritin assay were collected at approximately 6 weeks of age in the outpatient clinic. The blood was immediately centrifuged and the serum was separated into a sealed tube and was stored in deep freeze at −20°C till analysis was performed. Ferritin levels were done using Cobas E411-electrochemiluminescence immunoassay by Roche diagnostics.

Data collection

Baseline maternal data with regard to age, parity, body mass index (BMI), supplemental iron intake, Hb and hematocrit levels at delivery, postpartum hemorrhage (PPH) were collected. Infant data like birth weight, gestation, sex, 1 and 5 min Apgar Score, respiratory rates for the first 24 h, 24 h bilirubin, Hb, and hematocrit were recorded in all cases. Anemia at 24 h was defined as Hb <15 g/dl, polycythemia as hematocrit >65%, and hyperbilirubinemia as >15 mg/dl between 1 and 7 days of life. Normal serum ferritin at 6 weeks of age was taken as 200-600 ng/ml.

Statistical analysis

The data was entered in and analyzed using SPSS statistics for Windows, Version 17.0, Chicago, SPSS Inc. software. The descriptive statistics were expressed as mean and standard deviation for all the normally distributed continuous data and percentages for dichotomous and categorical data. The tests of significance used were independent sample t-test (parametric test) to compare the means of two groups of continuous variables and Chi-square test, nonparametric tests for categorical, and dichotomous data. Multiple regression was performed using the R Project for Statistical Computing Software.

Follow-up

Infants were closely monitored during the stay in hospital till discharge. Physicians in the postnatal wards took care of the babies as per neonatal unit routines. All babies were discharged after establishment of demand breastfeeding. Residential address and telephone numbers were collected maintaining confidentiality and used for following-up routinely. Mothers of the infants included in the study were contacted through telephone every 2 weeks to ensure exclusive breastfeeding, check bowel, bladder habits, and any requirement of hospitalization.


  Results Top


A total of 1088 deliveries took place during April 2012-March 2013 in Pondicherry Institute of Medical Sciences. A sample size of 86 was calculated and mothers were randomized into two groups at the time of delivery. 10 samples were hemolyzed and hence a total of 76 cases were analyzed for the outcome (ECC = 39; DCC = 37) [Figure 1]. Maternal characteristics like gravida, age, hemoglobin and body mass index did not show any significant difference between the two groups [Table 1].
Figure 1: Trial chart

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Table 1: Maternal characteristics in ECC and DCC groups

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Newborn characteristics

Gestational age, gender, Apgar scores were similar in both groups [Table 2]. The birth weights of infants did not show any difference among ECC and DCC groups.
Table 2: Newborn characteristics in ECC and DCC groups

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Secondary outcomes and complications

Possible side effects of placental transfusion like polycythemia, jaundice and requirement of phototherapy, respiratory distress, were analyzed from blood samples taken at 24 h of life and monitoring on following days of hospital stay for any signs of respiratory distress, clinical jaundice, and plethora.

Hemoglobin level at 24 h was significantly higher in the DCC group as expected. Anemia was seen with greater frequency in the ECC group and so was polycythemia in the DCC group. Mean levels of hyperbilirubinemia were higher in the DCC group. However, need for phototherapy was not significantly different between both groups. No difference were noticed in the incidence of direct hyperbilirubinemia between two groups. Respiratory distress and tachypnea was monitored at 1, 6, and 12 h and was found to have no significant differences between the two groups. None of the babies from either group required hospitalization till 6 weeks of age [Table 3].
Table 3: Secondary outcomes and complication rates in ECC and DCC groups

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Out of 86 cases randomized and followed-up, 10 samples were lysed before analyzing the results. Of these, 6 were from the DCC group and 4 from ECC group. Hence, 76 samples were analyzed and was found that iron ferritin is significantly higher among DCC infants than ECC infants at 6 weeks of life. Mean ferritin in ECC group were 299 and was 399 ng/ml among DCC. Statistically significant difference were found between two groups with a P = 0.0001 and 95% confidence interval (−153.93−46.34).

Multiple regression was performed using the R Project for Statistical Computing Software (http://www.r-project.org/) with serum ferritin levels as the outcome of interest (dependent variable). The predictors (independent variables) included the primary intervention (ECC vs. DCC), which was coded as a contrast (i.e., DCC = +1 and ECC = −1). This coding reflects the group differences between ECC and DCC, where the hypothesis is that serum ferritin levels will be higher for the DCC group (i.e., +1) than the ECC group (i.e., −1). Other secondary covariates were included as predictors in the model in order to assess their effect on the outcome of interest. The multiple regression analysis revealed that only the primary intervention variable (ECC vs. DCC) was statistically significant t (64) =2.45, P < 0.05 [Table 4].
Table 4: Multiple regression with primary and secondary variables

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  Discussion Top


For over six decades, workers have realized that DCC may result in a reduction of iron deficiency anemia in infancy, [13] which may have tremendous public health implications. There is little agreement among doctors and midwives about the optimum time of cord clamping. From the turn of the 20 th century, emphasis has been placed on ECC to facilitate giving of uterotonic to the mother, to prevent PPH or for neonatal resuscitation. [6] Clamping of the cord in <10-20 s after delivery is considered early clamping. Delayed clamping ranges from 1 to 3 min [14] or till the cessation of cord pulsation. [15] Level of the baby in relation to placenta also influences transfusion as shown by Yao and Lind. [8] In this study, the baby was held at a distance of 10 cm below the introitus.

One of the main concerns among obstetricians in performing DCC is the risk of PPH, especially in developing countries where anemia is prevalent. Data on the prevalence of PPH in DCC has not been consistent in earlier reports. Andersson et al. have found the duration of third stage was comparable and no difference in incidence of PPH between both groups. [5] In this study, only one mother developed PPH in the DCC group.

Delayed cord clamping results in transfusion of at least 55-180 ml of blood in the first few minutes of life based on indirect measurements based on increased weight in DCC babies. [5],[8] In our study, the birth weight did not show any significant difference between the two groups whereas others [6] have shown 101-150 g increase in the DCC group. Parameters like 1 and 5 min Apgar scores did not show any difference between the two groups in our study.

Number of days in hospital and admission to special care nursery did not show any difference. Which has been borne out by other workers as well. [6],[11]

Total bilirubin was done in all cases at 24 h and was higher in DCC which was significant, but that did not reflect in a significant increase in phototherapy. Three infants required phototherapy in the ECC versus 7 in DCC but there was no significant statistical difference. There have been varied reports about increase in hyperbilirubinemia and need for phototherapy, [16] but subsequent studies have clearly shown that neonatal hyperbilirubinemia is not a clinical problem in DCC. [5],[7],[17] There were no cases of direct hyperbilirubinemia in both groups of this study.

Hematological parameters studied were Hb and hematocrit levels 24 h and both were found to be significantly higher in the DCC group. This has been extensively documented by others. [7],[13],[17] However, when Hb and hematocrit were repeated at 4 months Andersson et al. [5] found no difference between both groups. This is not surprising as these are late markers of deficient body iron stores. Mothers with Hb levels of <10 g/dl were excluded in the present study but Gupta and Ramji found that even infants of anemic mothers (<10 g/dl Hb) had increased iron stores at 3 months of age in the DCC group. [12]

Polycythemia was seen in nil cases in ECC and two cases in DCC. Anemia was more common in ECC at 24 h of age. This has been reported by others. [5]

Serum ferritin at 6 weeks of age was the primary outcome measure and this showed a statistically significant increase in the DCC group. This has been repeatedly demonstrated in large trials and meta-analyses. [4],[5] Serum ferritin levels have shown an increase without much change in Hb and hematocrit values at 4 months of age [5] in the DCC group. Two studies from India however do not demonstrate the benefit of DCC for preventing anemia [3],[18] in term babies. The results of the multiple regression analysis confirm that there is a clear relationship between DCC and serum ferritin levels after accounting for the effect of secondary variables (e.g., maternal age, BMI, Hb, neonatal gestational age, birth weight, etc.).


  Conclusion Top


This study shows that DCC improves serum ferritin levels at 6 weeks of age in exclusively breastfed infants with no significant risk of hyperbilirubinemia/respiratory distress/polycythemia/postpartum bleeding. Thus, DCC should become the standard of care in all low risk singleton pregnancies.

 
  References Top

1.
Brabin B, Prinsen-Geerligs P, Verhoeff F, Kazembe P. Anaemia prevention for reduction of mortality in mothers and children. Trans R Soc Trop Med Hyg 2003;97:36-8.  Back to cited text no. 1
    
2.
Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131:649S-66.  Back to cited text no. 2
    
3.
Geethanath RM, Ramji S, Thirupuram S, Rao YN. Effect of timing of cord clamping on the iron status of infants at 3 months. Indian Pediatr 1997;34:103-6.  Back to cited text no. 3
    
4.
Chaparro CM, Neufeld LM, Tena Alavez G, Eguia-Líz Cedillo R, Dewey KG. Effect of timing of umbilical cord clamping on iron status in Mexican infants: A randomised controlled trial. Lancet 2006;367:1997-2004.  Back to cited text no. 4
    
5.
Andersson O, Hellström-Westas L, Andersson D, Domellöf M. Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: A randomised controlled trial. BMJ 2011;343:d7157.  Back to cited text no. 5
    
6.
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 Syst Rev 2013;7:CD004074.  Back to cited text no. 6
    
7.
Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in full-term neonates: Systematic review and meta-analysis of controlled trials. JAMA 2007;297:1241-52.  Back to cited text no. 7
    
8.
Yao AC, Lind J. Placental transfusion. Am J Dis Child 1974;127:128-41.  Back to cited text no. 8
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9.
Yao AC, Lind J, Vuorenkoski V. Expiratory grunting in the late clamped normal neonate. Pediatrics 1971;48:865-70.  Back to cited text no. 9
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10.
Saigal S, Usher RH. Symptomatic neonatal plethora. Biol Neonate 1977;32:62-72.  Back to cited text no. 10
[PUBMED]    
11.
Van Rheenen P, Brabin BJ. Late umbilical cord-clamping as an intervention for reducing iron deficiency anaemia in term infants in developing and industrialised countries: A systematic review. Ann Trop Paediatr 2004;24:3-16.  Back to cited text no. 11
    
12.
Gupta R, Ramji S. Effect of delayed cord clamping on iron stores in infants born to anemic mothers: A randomized controlled trial. Indian Pediatr 2002;39:130-5.  Back to cited text no. 12
    
13.
Lanzkowsky P. Effects of early and late clamping of umbilical cord on infant's haemoglobin level. Br Med J 1960;2:1777-82.  Back to cited text no. 13
[PUBMED]    
14.
Ceriani Cernadas JM, Carroli G, Pellegrini L, Ferreira M, Ricci C, Casas O, et al. The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life: A randomized, controlled trial. Arch Argent Pediatr 2010;108:201-8.  Back to cited text no. 14
    
15.
Van Rheenen PF, Brabin BJ. A practical approach to timing cord clamping in resource poor settings. BMJ 2006;333:954-8.  Back to cited text no. 15
    
16.
McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev 2008;2:CD004074.  Back to cited text no. 16
    
17.
Emhamed MO, van Rheenen P, Brabin BJ. The early effects of delayed cord clamping in term infants born to Libyan mothers. Trop Doct 2004;34:218-22.  Back to cited text no. 17
    
18.
Mathew JL. Timing of umbilical cord clamping in term and preterm deliveries and infant and maternal outcomes: A systematic review of randomized controlled trials. Indian Pediatr 2011;48:123-9.  Back to cited text no. 18
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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International Journal of Nursing Studies. 2019; 92: 97
[Pubmed] | [DOI]



 

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