COMPARISON OF LOCAL APPLICATION

OF CHLORHEXIDINE VS DRY CORD CARE

IN NEONATES DELIVERED IN TERTIARY
CARE HOSPITAL IN PREVENTING
OMPHALITIS

By

Muhammad Mohsan Ali

for

MD PEDIATRIC MEDICINE

under supervision of

Professor Dr Tayyaba Khawar Butt (MBBS, FCPS, MRCPCH)

(HEAD OF DEPARTMENT, PEDIATRIC MEDICINE UNIT I)

Services Institute of Medical Sciences, Lahore

 UNIVERSITY OF HEALTH
Title of Research Project:
Comparison of local application of chlorhexidine vs dry cord care in neonates delivered in tertiary care
hospital in preventing omphalitis

Synopsis submitted for: Discipline:

M.D. Pediatric Medicine

Name of the Applicant as per UHS Registration Record: Date of Birth.

Muhammad Mohsan Ali 04-10-1992

University Registration Number:

2010-SIMS-0171-UHS

Nationality: CNIC #:
Pakistani 36401-4115197-5

Address:

Room # 56, Doctors Hostel Services Hospital, Lahore.

Phone #: Email:
03046585891 drmohsan44@gmail.com

Qualifications (list all; with date of graduation):

MBBS Feb 2016 Services Institute of Medical Sciences, Lahore
F. Sc August 2007 Govt. Post graduate College Sahiwal
Matric July 2007 GHSSQaboola
Practical Experience (list all; with dates of employment):
1 M.D Pediatric Peads Unit-I, Services Hospital Lahore 14-02-2019 to till date

2 House Physician Peads Unit-I, Services Hospital Lahore 07-05 -2016 to 06-08-2016

3 House Surgeon Surgical Unit-I, Services Hospital Lahore 07-08-2016 to 06-11-2016

4 House Physician Medical Unit-II, Services Hospital Lahore 07-11-2017 to 06-02-2017

5 House Surgeon Pediatric Surgery, Services Hospital Lahore 07-02-2017 to 06-05-2017

Name of post-graduate institution, where applicant is currently studying

Services institute of medical sciences/Services hospital Lahore

Name of parent institution (if on deputation):

Name of Research Supervisor Signature: Date:

Professor Dr Tayyaba Khawar Butt

Name of Research Co-Supervisor (if any)

Name of Head of Department Signature: Date:

Professor Dr Tayyaba Khawar Butt

Name of Principal/Dean/Head of the institution Signature: Date:

Convener, Institutional Ethical Review Signature: Date:

Committee

Dr Khadija Irfan Khawaja

 Table of Contents:

Table of Contents
Project summary ..........................................................................................................................................7
Introduction .............................................................................................................................................8
Literature review ......................................................................................................................................9
Hypothesis .................................................................................................................................................11
Null hypothesis .......................................................................................................................................11
Alternate hypothesis ...................................................................................................................................11
Objective ...................................................................................................................................................12
Operational definition ............................................................................................................................13
Material and methods ............................................................................................................................14
Study design............................................................................................................................................14
Setting .........................................................................................................................................................14
Duration of study ...................................................................................................................................14
Sample size ..................................................................................................................................................14
Sampling technique.................................................................................................................................14
Inclusion criteria ..........................................................................................................................................14
Exclusion criteria .....................................................................................................................................14
Data collection procedure ...........................................................................................................................15
Data analysis ...........................................................................................................................................16
Outcome and utilization .........................................................................................................................17
Limitations .............................................................................................................................................18
Bibliography ...........................................................................................................................................19
Ethical declaration ..................................................................................................................................21
Consent (English) ....................................................................................................................................22
Estimated cost of project ........................................................................................................................24
Questionnaire ........................................................................................................................................25
Plan of work (Gantt chart) ......................................................................................................................26
List of Abbreviations:

CRP: C reactive protein

NICU: Neonatal Intensive Care Unit
NMR: Neonatal Mortality Rate

Project Summary:
Umbilical cord infection (omphalitis) is a risk factor for neonatal sepsis and mortality in low-resource settings

where home deliveries are common. Up to half of neonatal deaths in high mortality settings are due to

infections, many of which can originate through the freshly cut umbilical cord stump. The aim of this study is

to compare the outcome of application of chlorhexidine on umbilical cord versus dry cord care in neonates.

Neonates will be randomly allocated in two groups by using lottery method. The neonates in case group will

get an application of the 7% chlorhexidine digluconate gel (delivering 4% chlorhexidine) on cord stump on

their first day of life by the researcher and their mothers will be trained to do so once daily for first week of

life. Guardians or mother of the neonates in control group will be advised to keep the cord stump of their

neonates dry and clean without applying anything on it. They will be called for follow up on 14th day of life

and signs of omphalitis will be noted according to operational definition. Neonates who will develop

omphalitis, will be managed as per hospital protocol. The other outcome will be cord separation time and

incidence of neonatal sepsis. Data will be entered and analyzed by SPSS v25.0. Quantitative variables like

gestational age, weight of baby and cord separation time will be presented as Mean±S.D. Qualitative variables

like gender, residential area, socio-economic status, neonatal sepsis and omphalitis will be presented as

frequencies and percentages. Both groups will be compared for omphalitis and neonatal sepsis by using chi-

square test taking p-va1ue ≤0.05 as significant. Both groups will be compared for cord separation time by using

t-test taking p-va1ue ≤0.05 as significant.

Introduction:
Neonatal mortality is a major component of under-five childhood deaths in developing countries. About one

third of annual global neonatal deaths are caused by infections alone(McAllister et al., 2019). Tracking of

bacteria along the umbilical vessels in newly cut umbilical cord may lead to septicemia that can result in

neonatal morbidity and mortality, especially in developing countries(Stewart and Benitz, 2016). Pakistan has a

high neonatal mortality rate (NMR) of 53 per 1000 live births with sepsis as its major contributor (30% of

NMR)(Khan et al., 2019).

Unhygienic practices are prevalent in rural areas of the country. These include cutting the umbilical cord with

household knife, and applying unsafe substances like ash, crushed lead ore called surma, oil, turmeric and even

cow dung. This leads to high incidence of neonatal infections and deaths(Khanam et al., 2018). Chlorhexidine

is safe and inexpensive antiseptic and requires minimal training and skill and should strongly be considered for

adoption wherever home births occur(Mukunya et al., 2018).Studies have shown that chlorhexidine reduces

cord colonization with pathogens and thus omphalitis and sepsis. Omphalitis is a deadly infection of umbilical

cord and causes significant morbidity and mortality both historically and in areas where health care is less

readily available. Local data on this subject is available only in the form of a single published study, done in

rural areas of Dadu. Although it also shows the beneficial effects of this drug but results are variable in

different studies and this drug is not yet approved for cord care by local authorities in Pakistan due to non-

avai1ability and cost problems.

Through this study, we will collect more and accurate local evidence that 4% chlorhexidine is good enough, in

reducing omphalitis, to be adapted as standard operating procedure for newborn cord care in Pakistan. By

doing this study, we will be able to implement the regular use of chlorhexidine in Pakistan for newborn to

prevent risk of development of omphalitis in future.

Literature Review:

Unhygienic practices are prevalent in rural areas of the country. These include cutting the umbilical cord with

household knife, and applying unsafe substances like ash, crushed lead ore called surma, oil, turmeric and even

cow dung. This leads to high incidence of neonatal infections and deaths(Khanam et al., 2018). Chlorhexidine

is safe and inexpensive antiseptic and requires minimal training and skill and should strongly be considered for

adoption wherever home births occur(Mukunya et al., 2018).Studies have shown that chlorhexidine reduces

cord colonization with pathogens and thus omphalitis and sepsis.

A trial conducted by Sajid et al., in rural Pakistan showed that the rate of omphalitis was 3.2% with

chlorhexidine while 7.6% without chlorhexidine (dry cord). The factorial analysis indicated a reduction in risk

of omphalitis with chlorhexidine application (risk ratio [RR]=0.58, 95% CI 0.41-0.82; p=0.002)(Soofi et al.,

2012). El Arifeen et al., supported the evidence and reported that the rate of omphalitis was 18.5% with

chlorhexidine while 22.6% without chlorhexidine (dry cord). The difference was significant (p<0.005)(El

Arifeen et al., 2012).

Imdad A et al., observed that, chlorhexidine application on cord stump showed a reduction in omphalitis

ranged from 27% to 56% depending on the severity of the infection compared to dry care cord(Imdad et al.,

2013).Gathwala et al in North India showed that, chlorhexidine reduces neonatal sepsis in NICU when used on

umbilical cord(Gathwala et al., 2013).Rationale of this study is to compare the outcome of application of

chlorhexidine on umbilical cord versus dry cord care in neonates. Literature has shown that application of

chlorhexidine is beneficial in prevention of omphalitis.

Omphalitis is a deadly infection of umbilical cord and causes significant morbidity and mortality both

historically and in areas where health care is less readily available. Local data on this subject is available only

in the form of a single published study, done in rural areas of Dadu.Although it also shows the beneficial

effects of this drug but results are variable in different studies and this drug is not yet approved for cord care by

local authorities in Pakistan due to non-avai1ability and cost problems.

4% chlorhexidine significantly reduce the risk of umbilical infection in both single and multiple cord cleansing

groups as compared to clean and dry cord care group. (Khairruzaman et al.,2018) Dry cord care is effective in
countries with low infant mortality rate and in hospital births. However, 4% chlorhexidine for umbilical cord

care protects against omphalitis in home births, in countries with a high infant mortality rate. (Medina et

al.,2019) Chlorhexidine use was effective to lower neonatal omphalitis compared to those who received

dry cord care although cord detachment time was prolonged in former group. So it may be used regularly in our

common practice whether in hospital settings or in home births and it should be included as standard protocol

in essential newborn care in our setup where NMR is quite high (Ishaq et al.,2020).

The data was collected from 100 neonates. All the demographic values which include age, gender, gestational

age and mode of delivery were calculated. According to baseline values the birth weight of chlorhexidine

group was 1.87 ± 0.463 kg and dry cord group was 1.69 ± 0.421 kg. Umbilical sepsis is observed in only 1

patient in group I and in 3 patients in group II. Only single mortality was observed in group I and in 6 neonates

in group II. Conclusion: It is concluded that chlorhexidine umbilical cord care is more appropriate than the

currently WHO recommended dry cord care. (Mohsin et al.,2021)

Nine trials were included, from six countries: Zambia, Tanzania, Bangladesh, Nepal, India and Pakistan, with a

total of 257,153 participants. Five studies (N  =  119,833) reported neonatal mortality. There was a 21%

reduction in neonatal mortality among with 4% chlorhexidine application: pooled RR (95% CI) 0.79

(0.69–0.90), P  =  0.0005. The incidence of omphalitis was decreased by 35% with 4% chlorhexidine (6

studies, N  =  108,263): pooled RR (95% CI) 0.65 (0.56–0.75), P  =  0.00001. Chlorhexidine application delayed

the umbilical cord separation time (4 studies, N  =  28,917): mean difference (95% CI) 2.71 (2.63–2.78) days.

In conclusion, this systematic review found that topical application of 4% chlorhexidine to the umbilical cord

stump of newborn infants in lower income countries significantly reduces the incidence of neonatal mortality.

Chlorhexidine also reduces the incidence of omphalitis, but prolongs umbilical cord separation time. (Roba et

al.,2019)
Hypothesis:
NULL HYPOTHESIS

There is no difference in the incidence of omphalitis, cord separation time and neonatal sepsis with application

of chlorhexidine on umbilical cord versus dry cord care in neonates

ALTERNATE HYPOTHESIS

There is a difference in the incidence of omphalitis, cord separation time and neonatal sepsis with application

of chlorhexidine on umbilical cord versus dry cord care in neonates

Objectives:
To compare the incidence of omphalitis, cord separation time and neonatal sepsis with application of

chlorhexidine on umbilical cord versus dry cord care in neonates

Operational Definitions:
Omphalitis

It will be measured as the presence of redness, swelling (edema) and pus formation (any one or more) either on

the cord stump or the skin at the base of stump on clinical examination which will be done on 14th day of

experimental work.

Neonatal sepsis

Diagnosis of sepsis required presence of any two or more systemic inflammatory response syndrome criteria as

below:

 Fever (>38.3°C) or Hypothermia (core temperature < 36°C),

 Tachycardia (>180 bpm) or bradycardia (<100 bpm)

 Tachypnea (respiratory rate >60/min)

 Irritable or lethargic

 Abnormal white blood cell count or >10% immature bands.

Where infection is considered to be the underlying cause (raised CRP, urine pus cells>5, X-ray findings)

Positive blood /urine culture

Materials/Subjects & Methods:

Study Design: Randomized controlled trial

Setting: The study will be conducted at Department of Pediatrics Medicine, Services Hospital, Lahore.

Duration: Twelve months after the approval of synopsis

Sample Size:

Sample size of 96 patients (48 in each group) was estimated by 95% confidence level with 80% power of test

and taking expected percentage of sepsis as 2.86% with Chlorhexidine application and 21.43% in dry cord

care(Gathwala et al., 2013).

Z 1-α/2 = 95% = 1.96 (Gathwala et al., 2013)

Z 1-β = 80% = 0.80 (Gathwala et al., 2013)
P1 = 21.43% = 0.2143
P2 = 2.86% = 0.0286
P = P1-P2
n = 96
Sampling Technique: Non-probability consecutive sampling

Sample Selection:

Inclusion criteria:

 Neonates of both genders born and discharged on their first day of life from nursery

Exclusion criteria:

 Neonates admitted in the neonatal section of a health facility

 Neonates with obvious anomalies of cord or congenital defects (on clinical examination)

 Neonates having obvious morbidity at birth like birth asphyxia, poor Apgar score <7 at 5 minutes after

birth (on clinical examination)

  Early pre-term babies <34 weeks (as per date scan) and very low birth weight babies <2 kg (as recorded

by routine weight machine)

Methodology:
After approval from hospital ethical committee, neonates fulfilling inclusion and exclusion criteria will be

selected. Written informed consent will be obtained from the parents.

Neonates will be randomly allocated in two groups by using lottery method. The neonates in case group will

get an application of the 7% chlorhexidine gluconate gel (delivering 4% chlorhexidine) on cord stump on their

first day of life by the researcher and their mothers will be trained to do so once daily for first week of life.

Guardians or mother of the neonates in control group will be advised to keep the cord stump of their neonates

dry and clean without applying anything on it. They will be called for follow up on 14th day of life and signs of

omphalitis will be noted according to operational definition.

Neonates who will develop omphalitis, will be managed as per hospital protocol. The other outcome will be

cord separation time and incidence of neonatal sepsis. The data will be collected by researcher himself in a pre-

designed proforma (attached).

Statistical Analysis:
Data will be entered and analyzed by SPSS v25.0. Quantitative variables like gestational age, weight of baby

and cord separation time will be presented as Mean±S.D. Qualitative variables like gender, residential area,

socio-economic status, neonatal sepsis and omphalitis will be presented as frequencies and percentages. Both

groups will be compared for omphalitis and neonatal sepsis by using chi-square test taking p-va1ue ≤0.05 as

significant. Both groups will be compared for cord separation time by using t-test taking p-va1ue ≤0.05 as

significant.
Outcome & Utilization:
OUTCOME

1. Omphalitis will be measured as the presence of redness, swelling (edema) and pus formation (any one

or more) either on the cord stump or the skin at the base of stump on clinical examination.

2. Time of cord separation will be noted in days.

UTILIZATION

Result will help improve the better management of neonatal umbilical cord care and will help decrease the

incidence of neonatal omphalitis and sepsis.

Limitation of the proposed study:

 Single center study

 Limited sample size

Bibliography:
1. El Arifeen, S., Mullany, L.C., Shah, R., Mannan, I., Rahman, S.M., Talukder, M.R.R., Begum, N., Al-
Kabir, A., Darmstadt, G.L., Santosham, M. and Black, R.E., 2012. The effect of cord cleansing with
chlorhexidine on neonatal mortality in rural Bangladesh: a community-based, cluster-randomised
trial. The Lancet, 379(9820), pp.1022-1028.
2. Gathwala, G., Sharma, D. and Bhakhri, B.K., 2013. Effect of topical application of chlorhexidine for
umbilical cord care in comparison with conventional dry cord care on the risk of neonatal sepsis: a
randomized controlled trial. Journal of tropical pediatrics, 59(3), pp.209-213.
3. Imdad, A., Bautista, R.M.M., Senen, K.A.A., Uy, M.E.V., Mantaring III, J.B. and Bhutta, Z.A., 2013.
Umbilical cord antiseptics for preventing sepsis and death among newborns. Cochrane Database of
Systematic Reviews, (5).
4. Khan, S., Zaheer, S. and Safdar, N.F., 2019. Determinants of stunting, underweight and wasting among
children< 5 years of age: evidence from 2012-2013 Pakistan demographic and health survey. BMC
public health, 19(1), pp.1-15.
5. El Arifeen, S., Mullany, L.C., Shah, R., Mannan, I., Rahman, S.M., Talukder, M.R.R., Begum, N., Al-
Kabir, A., Darmstadt, G.L., Santosham, M. and Black, R.E., 2012. The effect of cord cleansing with
chlorhexidine on neonatal mortality in rural Bangladesh: a community-based, cluster-randomised
trial. The Lancet, 379(9820), pp.1022-1028.
6. McAllister, D.A., Liu, L., Shi, T., Chu, Y., Reed, C., Burrows, J., Adeloye, D., Rudan, I., Black, R.E.,
Campbell, H. and Nair, H., 2019. Global, regional, and national estimates of pneumonia morbidity and
mortality in children younger than 5 years between 2000 and 2015: a systematic analysis. The Lancet
Global Health, 7(1), pp.e47-e57.
7. Mukunya, D., Haaland, M.E., Tumwine, J.K., Ndeezi, G., Namugga, O., Tumuhamye, J., Sommerfelt,
H., Rujumba, J., Tylleskar, T., Moland, K.M. and Nankabirwa, V., 2018. “We shall count it as a part of
kyogero”: acceptability and considerations for scale up of single dose chlorhexidine for umbilical cord
care in Central Uganda. BMC Pregnancy and Childbirth, 18(1), pp.1-9.
8. Soofi, S., Cousens, S., Imdad, A., Bhutto, N., Ali, N. and Bhutta, Z.A., 2012. Topical application of
chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural
district of Pakistan: a community-based, cluster-randomised trial. The Lancet, 379(9820), pp.1029-
1036.
9. Stewart, D., Benitz, W., Watterberg, K.L., Cummings, J.J., Eichenwald, E.C., Poindexter, B.B., Aucott,
S.W., Goldsmith, J.P., Puopolo, K.M. and Wang, K.S., 2016. Umbilical cord care in the newborn
infant. Pediatrics, 138(3).
10. Shane, A.L., Sánchez, P.J. and Stoll, B.J., 2017. Neonatal sepsis. The lancet, 390(10104), pp.1770-
1780.
11. Khairuzzaman, M., Rouf, M.A., Sarker, M.M.A., Hossain, I., Matin, A., Mowla, G., Sarker, N.R.,
 Mannan, M.A. and Shahidullah, M., 2018. Chlorhexidine Cleansing of the Umbilical Cord for
Prevention of Umbilical Infection: A Hospital based Study in Bangladesh. Bangladesh Journal of Child
Health, 42(1), pp.4-8.
12. López-Medina, M.D., Linares-Abad, M., López-Araque, A.B. and López-Medina, I.M., 2019. Dry care
versus chlorhexidine cord care for prevention of omphalitis. Systematic review with meta-
analysis. Revista Latino-Americana de Enfermagem, 27.
13. Ishaq, F., Jamil, A., Sajjad, M., Iftikhar, M., Zafar, M.A. and Anwar, A., 2020. Efficacy of 4%
chlorhexidine in preventing neonatal umbilical cord infection. Journal of Fatima Jinnah Medical
University, 14(03), pp.136-139.
14. Riaz, N., Tahir, R., Muntaha, S.T., Aziz, S. and Zulfqar, R., 2019. Comparison of Umbilical Cord Care:
chlorhexidine 4% versus dry cord care. Journal of Islamic International Medical College
(JIIMC), 14(1), pp.8-12.
15. Mohsin, R., Khan, P. and Naveed, M., 2021. Use of Chlorhexidine on Umbilicus in Prevention of
Neonatal Sepsis.
16. Roba, A.A., Tefera, M., Worku, T., Dasa, T.T., Estifanos, A.S. and Assefa, N., 2019. RETRACTED
ARTICLE: Application of 4% chlorhexidine to the umbilical cord stump of newborn infants in lower
income countries: a systematic review and meta-analysis. Maternal Health, Neonatology and
Perinatology, 5(1), pp.1-9.
 Ethical Declaration

I undertake that: -

1. I will abide by the declaration of World Medical Association (WMA) made at Helsinki year 2013

regarding the ethical principles for medical research involving human subjects.

2. Informed consent of the patient or guardian shall be obtained after explaining any risk involved in the

procedure.

3. The health of the patients will be the prior consideration.

4. The procedures shall be kept aseptic and painless.

5. The patient shall be assured confidentiality of the findings.

Candidate signature: Supervisor signature:

Dr. Muhammad Mohsan Ali

Resident MD Pediatrics
Services Hospital, Lahore.
 CONSENT FORM

Research Participant Consent Form for Research Project

Services Hospital, Lahore

Serial no. Date Study centre

Name of project: comparison of local application of chlorhexidine vs dry cord care in neonates delivered

in tertiary hospital in preventing omphalitis

Name of Research supervisor: Pro Dr. Tayyaba Khawar Butt

Designation: Head of department Pediatrics unit I, SIMS/Services Hospital,
Lahore.
Name of research in charge: Dr. Muhammad Mohsan Ali
Department: Department of Pediatrics Unit-I, Services Hospital, Lahore.
Contact No.: 0304-658591

Purpose: To compare the outcome of application of chlorhexidine on umbilical cord versus dry cord care in

neonates

Procedure: Every patient will be explained the purpose of the study and requested to give her consent for

participation.

Time: 10 to 15 minutes will be required for every participant to participate in this study.

Possible Benefits: All the tests of the patients participated in this study will be guided for treatment.

Financial Consideration: There will be no financial burden on the patient. The financial benefits gained will

be free of cost testing for the participant.

Confidentiality: All the records will be confidential and identity will be treated with confidentiality. The result

of the study will be published for scientific purpose.

Termination from Participation: Every patient will have all the rights of getting excluded from the study

even if the consent form is signed.

S/O, D/O I have been informed

about the details and application of the study. I understand completely. I understand that the study will not

involve me with hazards. I have gone through the contents of the Performa and I am willing to cooperate for

the completion of this data.

1. Name of Patient

2. Signature of patient

3. Name and signature of guardian

4. Name and signature of Research in charge

ESTIMATED COST OF THE PROJECT

Items Units Unit price Total cost (Rs.)

Stationary 300 pages+30 30 9900
pencils
Chlorhexidine gel 50 94 4700
Miscellaneous 5 230 1150
Total cost 15,750/=
 PLAN OF WORK

1ST 2ND – 7TH 8TH -10TH 11TH -12TH

TASK
MONTH MONTH MONTH MONTH

Synopsis approval

Data collection

Data entry &

analysis

Thesis writing &

submission
 PROFORMA

COMPARISON OF LOCAL APPLICATION OF CHLORHEXIDINE VS DRY CORD CARE IN

NEONATES DELIVERED IN TERTIARY CARE HOSPITAL IN PREVENTING OMPHALITIS

Date: ________________ Registration No: __________________________________

Name: _______________________________________________________________

Address: _____________________________________________________________

Groups: Chlorhexidine Dry Care

Gender: Male Female

Gestational Age: _____________

Birth Weight: _______________

Socio-economic status: Low (<20,000/month)

Middle (20-50,000/month) High (>50,000/month)

Residential area: Rural Urban

OUTCOME

Omphalitis (within 14 days): Present Absent

Neonatal sepsis: Present Absent

Cord separation time: __________ (days)