INTEGRATIVE REVIEW 1

Integrative Review

Danielle Klement

Bon Secours Memorial College of Nursing

Dr. Arlene Holowaychuk EdD, MSN, RN, CNE

Nursing Research NUR 4122

October 17, 2018

“I Pledge…”
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Abstract

The purpose of this integrative review is to evaluate literature pertaining to delayed cord clamping

(DCC) in preterm neonates and its influence on their outcomes. Immediate cord clamping (ICC)

is usually performed after birth however studies have shown delayed cord clamping can improve

neonatal outcomes. The PICO question being considered is: In preterm neonates, what is the effect

of delayed cord clamping on neonatal outcomes in comparison to immediate cord clamping?

Databases such as EBSCO Discovery Services and PubMed were utilized to locate research

articles. The results yielded 2,899 research articles and five of them satisfied the research criteria.

The research design is an integrated review. Two of the five research groups identified that after

implementing DCC on neonates, their hematocrit levels were significantly higher than those who

implemented ICC. The remaining three articles found that there were no major differences or

serum ferritin levels were improved in the DCC groups. Implications of these studies suggested

that DCC had positive effects on temperature, hematocrit levels, iron levels, heartrate consistency,

improved blood pressures and urinary output. Limitations to this review include: student’s lack of

experience writing research papers and a short time frame to complete the assignment. Future

research should focus on long term effects of DCC on neonatal outcomes.

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Integrative Review

The purpose of this integrative review is to examine literature that evaluates the effect of

delayed cord clamping (DCC) on neonatal outcomes in preterm infants. In current practice

immediate cord clamping (ICC) is usually utilized after birth. The umbilical cord acts as a

conduit for gas exchange, homeostasis, and nourishment for the fetus. Therefore, DCC can

provide 25-35ml of blood for every kilogram in infants and this improves iron stores, which

leads to a reduction in anemia (Chopra, Thakur, Garg, Kler, & Gujral, 2018). The additional

blood volume also helps to perfuse the lungs, kidneys, intestines, and the skin. This makes

adaptation to extrauterine life more successful (Dipak, Nanavati, Kabra, Srinivasan, & Ananthan,

2017). Some studies have shown that DCC of preterm neonates results in improved health

conditions such as lower rates of respiratory distress, less morbidities, and lower risk of

hemorrhage (Armanian, Tehrani, Ansari, & Ghaemi, 2017). The researcher located a vast

majority of literature based on this topic, but there were some limitations surrounding literature

comparing DCC and ICC. The proposed PICO question to be considered is: In preterm neonates,

what are the effects of delayed cord clamping on neonatal outcomes in comparison with

immediate cord clamping?

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Design and Search Methods

An integrative review is the research method utilized. This review focuses on five

articles. The articles were found utilizing two search engines, EBSCO Discovery Service and

PubMed, to find applicable research. The key terms used consisted of, ‘delayed cord clamping’,

‘neonate’, ‘outcomes’, and ‘immediate cord clamping’. The search generated 2,426 articles from

EBSCO Discovery Service and 473 articles from PubMed demonstrating a significant amount of

research and literature on this topic. To ensure the articles would fit into the criteria of accepted

research, the search was limited to the last five years, 2013-2018, from peer-reviewed, are

quantitative, are offered in full text through the library databases, and are written in English. The

articles related to the researcher’s PICO question, ‘In preterm neonates, what are the effects of

delayed cord clamping on neonatal outcomes in comparison to immediate cord clamping?’ To

locate these articles inclusion and exclusion criteria were utilized. The inclusion criteria consists

of preterm newborns who received either delayed cord clamping or immediate cord clamping

following birth. If the articles did not meet the inclusion criteria, they were excluded. Based on

this screening, five quantitative research articles were identified and utilized for this integrative

review.

Findings/Results

The findings and results of the research clearly indicate a positive effect of implementing

DCC in preterm neonates as indicated by measurable outcomes (Chopra et al., 2018; Dipak et al.,

2017; Armanian et al., 2017; Chiruvolu, Daoud, & Inzer, 2018; Blank et al., 2018). A summary
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of the research articles is presented in the appendix. The researcher framed the review according

to the following categories: cardiovascular outcomes and time of cord clamping.

Cardiovascular Outcomes

In a quantitative, randomized control study conducted by Dipak et al. (2017), the authors

researched the importance of DCC on hemodynamic stability in preterm neonates. There were

three groups in this study, an early cord clamping (ECC) group and two DCC groups. The ECC

group consisted of 27 infants, the first DCC group contained 26 infants, and there were 25

infants in the second DCC group. Data was collected at birth and four hours after birth; including

hematocrit levels at four hours of age, the need for vasopressor support, RBC transfusions, and

sepsis onset. Data analysis was performed using the Statistical Package for the Social Sciences.

Significant findings were found between the groups. At four hours of age the mean venous

hematocrit was 47.6% in the ECC group and 58.7-58.9% in the DCC groups. Six infants in the

ECC group required vasopressor support, while three infants required it in the DCC groups.

Some RBC transfusions were needed among all groups, 11 infants from the ECC group and three

infants from the DCC group. The sepsis findings are not significant but there is slight difference.

Nine ECC infants developed late onset sepsis, whereas eight DCC infants developed it.

In another quantitative, randomized control trial by Chopra et al. (2018), neonatal

outcomes associated with hematocrit, hemoglobin, and ferritin levels are evaluated. Two groups

were compared in this study, an ECC group and DCC group. The ECC group contained 44

infants and the DCC group contained 38 infants. Data was collected at birth, two hours after

birth, and three months of age; including ferritin levels, hematocrit and hemoglobin levels. Data
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analysis was performed utilizing the Students t- test and the Chi-squared test. At three months of

age, serum ferritin levels were higher in the DCC group. The ECC groups mean level was

50.5ng/ml and the DCC groups mean level was 86ng/ml. The mean hemoglobin in the DCC

group was 10.18g/dl and the ECC group was 10.37g/dl. At two hours old, the mean hematocrit

levels were as follows: ECC group was 61.15% and the DCC group was 63.13%.

Chiruvolu et al. (2018), examined variables that would affect the neonatal outcomes of

twin preterm infants. This was a quantitative, retrospective cohort study. A historic group (ICC)

and DCC cohort were evaluated with 30 infants in the ICC group and 32 in the DCC group. The

data was obtained at birth and one week of age; including hematocrit levels and RBC

transfusions. Data analysis was performed using Chi-squared test, Generalized Linear Mixed

Models, and Students t-test. At birth, the ICC group’s mean hematocrit level was 43.2% and the

DCC group’s mean level was 48.1%. At one week of age, 13 infants in the ICC group required

RBC transfusions, whereas 5 infants in the DCC group required RBC transfusions.

Cord Clamping Timing

In a quantitative, non-randomized feasible cohort study conducted by Blank et al. (2017),

DCC effects on gas exchange was evaluated. There were two groups, a vigorous group of 32

infants and a non-vigorous group of 12 infants. The data was collected at birth; including

APGAR score, pH, PO2, and PCO2 levels. Data analysis was performed using Friedman’s test

with Bonterroni correction and IBM SPSS Statistics 24. The ECC group was clamped at 85

seconds. The DCC group was clamped anywhere from two to five minutes, depending on the

support needed.

The quantitative, randomized control study by Armanian et al. (2017) studied the effects

of DCC on preterm infants. This study contained two groups, a DCC and ICC group. Each group
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consisted of 30 infants. Data was collected at birth and four hours after; including APGAR score

and hematocrit levels. The data analysis was performed using the Chi-squared test, Mann-

Whitney test, and SPSS. The cord clamping of the ECC group occurred at 10-15 seconds after

birth. The DCC group’s clamping occurred at 30-45 seconds after birth. Hematocrit levels four

hours after birth were as follows: 49.6% in the DCC group and 46.6% in the ECC group.

Discussions and Implications

The results of the research articles discussed in this review clearly identify a positive

relationship between neonatal outcomes and preterm infants when DCC is implemented. Due to

that relationship, the research included in this review supports the PICO question set by the

researcher. Quantitative research by Chopra et al. (2018), Armanian et al. (2017), Dipak et al.

(2017), and Chiruvolu et al. (2018), support the PICO question by highlighting the importance of

DCC on neonatal outcome factors. These factors include hematocrit levels, iron stores, blood

pressure, temperatures, increased urinary output, and a reduced need for surfactant therapy. DCC

directly impacts many factors of neonatal outcomes in preterm neonates. While, not all the

results showed statistical significance pertaining to DCC, most expressed a trend in improving

many health conditions.

The implications of the findings suggest that preterm neonates could be positively

impacted by initiating DCC at birth. The extra blood volume infants receive during DCC is

associated with less hypothermia. To aide in better outcomes for preterm neonates DCC presents

a possible benefit for these at risk infants. Improvements should be made in further research on

this topic with larger sample sizes and greater diversity. Also longer follow-ups are needed to
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better understand the long term effects of DCC. There were plenty of articles on DCC itself but

not many based around preterm neonatal outcomes and in comparison, with ICC.

Limitations/Conclusion

Multiple limitations should be mentioned as a part of this integrative review. The

researcher does not have any prior experience in completing an integrative review. The short

amount of time to complete the review and the criteria of utilizing only five articles could be

considered limitations. Several of the studies mentioned overall limitations were small sample

size, no long term follow-ups, and data reported from a single center. Due to the small sample

size and use of a single center to obtain data, there is a need for more diversity within the

research. The articles utilized in this review were within the past five years. Chopra et al. (2018),

Dipak et al. (2017), Chiruvolu et al. (2018), and Armanian et al. (2017) determined that due to a

small sample size there were limitations to generalizability. All of the research articles utilized

either randomized or non-randomized study types. Within all the articles the variables were

clearly stated, and the validity of the tools were provided.

Findings discussed in the integrative review highlight the importance of implementing

DCC in preterm neonates for better health outcomes. Despite many studies suggesting DCC

provides significant benefits to infants in general, but especially preterm neonates, the optimal

cord clamping time in premature neonates is still controversial (Dipak et al., 2017). DCC should

be implemented to all infants but especially preterm neonates as long as no serious complications

arise. This could impact neonatal outcomes drastically. The implementation of DCC in preterm

neonates following birth is an important factor in the birthing process that needs further

addressing.
INTEGRATIVE REVIEW 9

References

Armanian, A., Tehrani, H. G., Ansari, M., & Ghaemi, S. (2017). Is "Delayed Umbilical Cord

Clamping" Beneficial for Premature Newborns? International Journal of Pediatrics,5,

4909-4918. doi:10.22038/ijp.2016.7909

Blank, D. A., Badurdeen, S., Kamlin, C. F., Jacobs, S. E., Thio, M., Dawson, J. A., . . . Davis, P.

G. (2018). Baby-directed umbilical cord clamping: A feasibility study. Resuscitation,131,

1-7. doi:10.1016/j.resuscitation.2018.07.020

Chiruvolu, A., Daoud, Y., & Inzer, R. W. (2018). Effect of delayed cord clamping on very

preterm twins. Early Human Development,22-25. doi:10.1016/j.earlhumdev.2018.08.002

Chopra, A., Thakur, A., Garg, P., Kler, N., & Gujral, K. (2018). Early versus delayed cord

clamping in small for gestational age infants and iron stores at 3 months of age- a

randomized controlled trial. BMC Pediatrics,1-6. doi:10.1186/s12887-018-1214-8

Dipak, N. K., Nanavati, R. N., Kabra, N. K., Srinivasan, A., & Ananthan, A. (2017). Effect of
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Delayed Cord Clamping on Hematocrit, and Thermal and Hemodynamic Stability in

Preterm Neonates: A Randomized Controlled Trial. Delayed Cord Clamping in Preterm

Neonates,54. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28285280.

 INTEGRATIVE REVIEW
First Author
(Year)/Qualifications
Background/Problem Statement
Conceptual/theoretical
Framework
Design/
Method/Philosophical
Underpinnings
Sample/ Setting/Ethical
Considerations
Major Variables Studied (and
their definition), if appropriate
Measurement Tool/Data
Collection Method
Data Analysis
Findings/Discussion
Appraisal/Worth to practice
11
Appendix
Chopra (2018)/ Department of Neonatology, Sir Ganga Ram Hospital, New Delhi, India.
DCC (delayed cord clamping) is the standard of care in infants not requiring resuscitation, however effects of
cord clamping strategies have not been evaluated systemically in SGA infants.
Researchers wanted to compare the effects of DCC and ECC (early cord clamping) on serum ferritin at 3 months in
SGA infants born >35 weeks.
 Quantitative
 Randomized controlled trial
 113 infants
 Sir Ganga Ram Hospital
 Informed consents obtained, exclusion of all participants names, and ethics committee approval
 DCC group of 38 infants- cord clamped 60 seconds after birth
 ECC group of 44 infants- cord clamped immediately after birth
 Antenatal sonography
 Screening pregnant women (evidence of fetal growth restriction)
 Blood samples
 Fisher exact or Chi square test
 Students t test or Mann Whitney test
 Infants in the DCC group had significantly higher serum ferritin levels compared to the ECC group
 Findings were in favor of the DCC group
 Infants with iron deficiency were lower in DCC group, could have important implications to countries with a
large population of SGA infants and at a high risk of iron deficiency
 DCC leads to improved iron stores in SGA infants >35 weeks at 3 months of age
 INTEGRATIVE REVIEW
First Author
(Year)/Qualifications
Background/Problem Statement
Conceptual/theoretical
Framework
Design/
Method/Philosophical
Underpinnings
Sample/ Setting/Ethical
Considerations
Major Variables Studied (and
their definition), if appropriate
Measurement Tool/Data
Collection Method
Data Analysis
Findings/Discussion
Appraisal/Worth to practice
12
Blank (2018)/ Newborn Research Centre, The Royal Women’s Hospital, Melbourne, Australia. The
Ritchie Centre, Hudson Institute of Medical Research, Monash University, Melbourne, Australia.
DCC (delayed cord clamping) is uncommon in non-vigorous infants due to difficulties in resuscitation, in
baby directed DCC the cord remains patent until the infant’s lungs are exchanging gases.
Researchers wanted to determine the feasibility of baby directed umbilical cord clamping in infants born >32
weeks gestation.
Theoretical framework was not mentioned.
 Quantitative
 Non-randomized, feasibility cohort study
 44 infants
 Royal Women’s Hospital in Melbourne, Australia
 Verbal permission from maternal care team, written consent from families obtained, and ethics
committee approval
 Vigorous group of 32 infants
 Non-vigorous group of 12 infants
 Ultrasounds to visualize infant’s heart rate
 ECG electrodes
 Blood samples
 APGAR scores
 Friedman’s test with Bonferroni correction
 IBM SPSS Statistics 24
 DCC infant’s heartrate remained more consistent than those who received ICC (immediate cord
clamping)
 This study adds to growing literature on this topic
 Researchers mention more studies with larger cohorts are needed to determine the risk of hypothermia
during DCC in term and preterm infants.
 Limitations: one method for heartrate monitoring and researchers did not prepare a sterile table for
supporting the infant.
 Small feasible study- doesn’t provide enough evidence of clinical benefit
 INTEGRATIVE REVIEW
First Author
(Year)/Qualifications
Background/Problem
Statement
Conceptual/theoretical The researchers wanted to determine the effect of delayed cord clamping on premature neonatal outcomes.
Framework Theoretical framework was not mentioned.
Design/Method/
Philosophical
Underpinnings
Sample/ Setting/Ethical
Considerations
Major Variables Studied
(and their definition), if
appropriate
Measurement Tool/Data
Collection Method
Data Analysis
Findings/Discussion
Appraisal/Worth to
practice
13
Armanian (2017)/ Associative Professor of Neonatology, Division of Neonatology, Department of Pediatrics, Child
Growth, and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
ICC (immediate cord clamping) is active management of the third stage of labor, but an unclamped umbilical cord
may cause inconvenience in preterm infants because they often need resuscitation.
 Quantitative
 Single- center randomized control trial study
 Comparing Apgar scores, hematocrit levels, intraventricular hemorrhage, and levels of resuscitation between DCC
infants and ICC infants
 60 premature infants
 Isfahan University of Medical Sciences at Alzahra and Shahid Beheshti Hospitals
 Informed consent was obtained from the parents
 DCC group of 30 infants
 ICC group of 30 infants
 Blood samples
 APGAR scores
 Echocardiogram
 Brain ultrasound
 Chi-square test or Fisher’s exact test
 Mann-Whitney Test
 Statistical Package for the Social Sciences was used
 Neonates who received DCC had significantly higher hematocrit levels after 4 hours of birth compared to infants who
received ICC
 Higher rates of sepsis in ICC group
 Researchers suggest further research needs to be done with a larger sample size and longer follow-up to validate the
findings
 The results of this study were favorable of DCC
 INTEGRATIVE REVIEW
First Author
(Year)/Qualifications
Background/Problem
Statement
Conceptual/theoretical The researchers wanted to evaluate the short term effects of DCC on preterm neonates.
Framework Theoretical framework was not mentioned.
Design/Method/
Philosophical
Underpinnings
Sample/ Setting/Ethical
Considerations
Major Variables Studied
(and their definition), if
appropriate
Measurement Tool/Data
Collection Method
Data Analysis
Findings/Discussion
14
Dipak (2017)/ Department of Neonatology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India
Optimal cord clamping time for premature infants still remains controversial. DCC is considered a physiological
mechanism by which the newborn may receive additional blood volume to help perfuse the lungs, intestines, kidneys,
and the skin.
 Quantitative
 Randomized controlled trial
 Comparing temperatures, urine output, hematocrit, and blood pressure between DCC and ECC infants.
 78 premature infants
 Neonatal Unit at KEM hospital, Parel, Mumbai, India
 Informed consent was obtained from the mothers
 IRB approval
 DCC group 1 of 26 infants
 DCC group 2E of 25 infants (these mothers received ergometrine IM)
 ECC group of 27 infants
 Blood samples
 APGAR scores
 Axillary temperatures were taken at 5 minutes post delivery
 Non-invasive BP
 CRIB (clinical risk index for babies) score
 Retinal exams
 SPSS used
 Venous hematocrit levels at 4 hours after birth were significantly higher in the DCC groups in comparison to the ECC
group
 DCC group had improved temperatures on admission to NICU
 Limitation: researchers did not measure effects of DCC on blood volume and only recording the short term effects.
Also single-center based study and a small sample size.
 DCC is associated with less hypothermia on admission to the NICU and improved blood pressure and increased
urinary output
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 Recommends further studies with larger sample sizes

Appraisal/Worth to  The results of this study were favorable of DCC
practice
 INTEGRATIVE REVIEW
First Author
(Year)/Qualifications
Background/Problem
Statement
Conceptual/theoretical The researchers wanted to report the consequences of DCC in preterm twins.
Framework Theoretical framework was not mentioned.
Design/Method/
Philosophical
Underpinnings
Sample/ Setting/Ethical
Considerations
Major Variables Studied
(and their definition), if
appropriate
Measurement Tool/Data
Collection Method
Data Analysis
Findings/Discussion
16
Chiruvolu (2018)/ Division of Neonatology, Department of Pediatrics, Baylor University Medical Center, Pediatrix
Medical Group, Dallas, Texas.
Preterm infants of twin births may particularly benefit from DCC due to the likelihood of unfavorable outcomes is
greater compared to single births. However, there is not enough information regarding the safety and efficacy of
DCC.
 Quantitative
 Retrospective cohort study
 Comparing Apgar scores, hematocrit levels, intraventricular hemorrhage, and levels of resuscitation between DCC
infants and ICC infants
 62 premature infants
 Baylor University Medical Center, Dallas, Texas
 Informed consent was obtained from the parents
 IRB approval
 30 infants in ICC group (historic cohort)
 32 infants in DCC group
 Blood samples
 APGAR scores
 Maternal demographics
 Temperatures on admission
 Student t-test
 Chi-squared or Fisher exact test
 Generalized Linear Mixed Models
 Statistical analyses were performed with JMP and SAS Enterprise Guide software
 No major differences in APGAR scores, temperatures, or initial hematocrit within both groups
 Significantly fewer infants within the DCC group needed RBC transfusions in comparison to the ICC group
 Fewer infants in the DCC group received surfactant therapy for RDS in comparison to the ICC group
 Limitation of generalizability due to the small sample size and the data was reported from a single center
 Recommend further, larger clinical studies
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Appraisal/Worth to practice  The results of this study were in favor of the DCC group
 DCC in preterm twins was safe, feasible, and not associated with any adverse neonatal outcomes when compared to
ECC.