Nigerian Journal of Paediatrics

Methylated spirit versus 4 chlorhexidine gel in neonatal umbilical cord infection A short report of a randomized open labelled parallel group trial

Niger J Paediatr 2018; 45 (2):118 - 122

ORIGINAL

Shwe DD

CC – BY Methylated spirit versus 4%

Abok II

Diala UM

chlorhexidine gel in neonatal

Egbodo C

umbilical cord infection: A short

Toma BO

report of a randomized, open-

Nathan S

Pam VC

labelled, parallel-group trial

Ocheke A

Oguche S

DOI:http://dx.doi.org/10.4314/njp.v45i2.8

Accepted: 3rd May 2018

Abstract : Background: Neonatal

JUTH, 33(64.7%) were males with

sepsis is a known leading cause of

a mean birth weight of 3.7kg (CI

Shwe DD (

)

neonatal morbidity and mortality.

3.04 – 3.30). Mean cord separation

Abok II, Diala UM, Toma BO

Aim: To compare the efficacies of

times were 7.96 ± 4.07)days in the

Oguche S

96% methylated spirit and 4%

methylated spirit group vs 6.43 ±

Department of Paediatrics,

chlorhexidine (CHX) gel in the

3.13days in the CHX comparator

treatment of umbilical stump of

group,

(p=0.078).

Omphalitis

Egbodo C, Pam VC, Ocheke A

neonates.

was0% vs 2(8.3%) and NNS 2

Department of Obstetrics and

Method: This was a randomized,

(7.4%) vs 2(8.3%) in methylated

Gynaecology,

open labelled, parallel group trial

spirit and CHX treatment groups

of CHX gel and Methylated spirit

respectively. There was 1(3.7%)

Nathan S

for neonatal umbilical cord care in

mortality in the methylated spirit

Department of Internal Medicine,

Jos, between 2/6/17 and 16/7/17.

treatment group.

University of Jos/Jos University

Inclusion criteria were term,

Conclusion: Methylated spirit and

Teaching Hospital

newly born 0 to 6 hours old, with

4% CHX gel have comparable

Email: shwedavid@yahoo.com

no known risk for sepsis and writ-

umbilical stump treatment effi-

ten informed parental consent.

cacy. Methylated spirit may be a

**** Fertile Ground Hospital and

Eligible subjects were randomized

safe alternative in clinical settings

IVF Center, Zaramaganda, Jos,

to receive methylated spirit or 4%

where topical 4% CHX gel is un-

Plateau State.

CHX gel. Outcome measures

available or unsafe.

were cord separation time, om-

phalitis, neonatal sepsis and neo-

Key words: Methylated spirit, 4%

natal mortality by day 28.

Chlorhexidine gel, mortality, Cord

Results: A total sample of 51 of

separation time, Neonatal sepsis,

58 met enrolment criteria. Thirty-

Omphalitis

two (62.7%) where delivered in

Introduction

cord stump in settings of poor environmental hygiene or

where neonatal mortality is high. On November 17 ,

Neonatal sepsis (NNS) is a public health burden in sub-

2016, the Federal Ministry of Health, Nigeria published

Saharan Africa (sSA). In 2015, the World Health Or-

and rolled-out a 5 year National Strategy for Scale – up

of CHX gel for the care of umbilical cord in Nigeria.

ganization (WHO) Global Health Observatory (GHO)

reported 2.7 million neonatal deaths of which 7% was

However, the wide spread use of CHX has been grossly

attributable to NNS. Omphalitis is significant focus for

made difficult by its unavailability, acceptability and

NNS particularly in developing countries.

2,3,4

effectiveness in Nigeria. To the best of our knowledge,

Four percent ethyl alcohol, commonly identified as me-

there are few studies comparing its efficacy with methy-

thylated spirit (surgical spirit) is a denatured alcohol

lated spirit which has been in use in our clinical setting

which has been in use for the care of umbilical cord for

for a very long time.

a long time, perhaps partly because is effective, readily

available and affordable in most parts of the world.

5, 6

At the moment, topical 4% CHX gel is the goal standard

Recent studies seem to suggest that, use of topical 4%

for the care of umbilical cord of newborns and thus,

chlorhexidine gel (CHX) is superior to methylated spirit

presents a strong challenging comparator to other topical

in reducing incidence of omphalitis among newborns.

agents. Therefore, this short report aims to compare the

Consequently, WHO advocated and deployed wide

efficacies of methylated spirit and 4% CHX in the um-

spread use of topical 4% CHX for the care of umbilical

bilical cord care for prevention of omphalitis and or

119

NNS in healthy hospital born neonates in Jos, Plateau

topical application of test agents and proper hand-

State, Nigeria.

washing technique.

Four per cent topical CHXgel was applied generously on

the umbilical stump and spread around the abdominal

wall area that comes into contact with the stump using

Methodology

the index finger. This was carried out twice daily and

any other times of the day the stump appeared wet. On

Study design: A Randomized, open-labelled, Parallel-

the other hand, clean piece of cotton wool soaked in

group Trial of methylated spirit and topical 4% CHX

dispensed 50mls container of 96% methylated spirit was

gel.

used in cleaning of stump and the cord clamp every two

Study participants: Apparently healthy term hospital

hours. Cleansing procedure started from the tip of the

born neonates with no known risk factors for NNS were

stump towards the cord clamp and proximally to the

identified for enrollment.

base of the stump. Care-givers were also provided with

Study locations: The study was conducted in the Jos

more test agents whenever they were exhausted.

University Teaching Hospital (JUTH) and Fertile

Eligible enrollees were then allocated to one of the treat-

Ground Hospital (FGH), both of which are located in the

ment groups by simple random technic (1:1).

cosmopolitan city of Jos, Plateau State, and provide ma-

ternal and newborn health services.

Caregivers had telephone interviews on day 2 following

The Jos University Teaching Hospital is a 500 bed ca-

enrolment into the study. Information of interest on the

pacity tertiary centre with an average of 2809 deliveries

checklist were: fever, redness around cord stump, bleed-

per annum. Fertile Ground Hospital on the other hand, is

ing, bad odor or purulent discharge, swelling, frequency

a privately owned 29 bed capacity and multi-specialist

of cord care, cord separation time, evidence of omphali-

hospital which in addition, provides in-vitro - fertiliza-

tis and or sepsis. Questions were also solicited for use of

tion (IVF) services. It has an average of 296 annual de-

other agents out of study protocol. Enrollees had re-

liveries.

turned visits on days 7, 14 and 28 or any other days

within study protocol when there were study related

Enrolment criteria

concerns. On each clinic visit, clinical evaluation was

Inclusion criteria:

Apparently healthy term hospital

carried out for evidence of cord separation, omphalitis or

born, male and female newborns ≥ 0 to ≤ 6 hours

sepsis. In the event of diagnosis of probable sepsis,

With written informed consent of parent or legally ac-

based on WHO Guidelines for omphalitis (erythema,

ceptable representative (LAR) and their willingness for

foul smelling discharge around the cord), the patient

return visits to delivery hospital or telephone interview

were hospitalized in the respective health facility. Blood

per study protocol.

culture, cord swab and lumber puncture for cerebrospi-

Exclusion criteria: Structural birth defects where topical

nal fluid microbiological diagnosis were carried out. The

application of test agent is impossible (e.g. omphalocele,

affected neonates received our hospital’s standard of

gastroschisis), clinical or laboratory evidence of sepsis,

care for NNS therapy.

maternal peripartum pyrexia, prolonged rupture of fetal

membranes or evidence of chorioamnionitis, HIV/HBV/

Cord separation time: This was defined as the time

HCV seropositive mothers and known hypersensitivity

(days) taken for the umbilical cord to dry and com-

to any of the topical test agents.

pletely fall off from the cord stump.

Solicited adverse reactions such as dermatitis, anaphy-

laxis were recorded on CRF.

11,12

Intervention

Any study subject who

Test agents

developed such reactions were given alternative treat-

ment.

Topical Chlorhexidine digluconate 7.1% (equivalent to

Protocol violation: A study subject was judged to have

4% chlorhexidine gel): 4% CHX (25g of 4% Chlorxy-G

violated protocol if there is evidence to suggest: Use or

Gel, Batch N0 CGH2, manufactured date: 08/15 and

application of a different treatment agent outside study

expiry date: 07/18) for application on cord stump ac-

protocol, umbilical stump was cut manually for any rea-

cording to manufacturer’s instructions.

son and or did not apply treatment agent according to

Topical 96% methylated spirit: This was obtained from

protocol.

the Compounding Pharmacy Unit of the Jos University

Teaching Hospital.

Outcome measures

Subjects identification, screening and enrollment proce-

dures

The primary out come measure was cord separation time

Prior to enrollment, full clinical history was obtained

(days). The secondary outcomes were development of

and thorough physical examination carried out. Relevant

omphalitis, NNS and occurrence of mortality until

medical information obtained (age, sex, gestational and

D28.Adverse reactions to test agents were documented.

mode of delivery, risk for sepsis, history of sensitivity to

test agent, maternal age, parity, vaccination status,

Statistical Analysis

weight, temperature, structural defect) were documented

on case report forms (CRF). Care-givers were taught in

Primary analysis was performed on Day 28 per protocol

addition to clinical demonstration, the procedure for

population (PP) of neonates. The intention to treat (ITT)

120

study subjects were all treatment allocated neonates who

into one of the treatment groups to receive 96% methy-

had at least one topical application of test medication.

lated spirit or 4% chlorhexidine gel. Two subjects

Per protocol population was a subset of the ITT as well

(6.9%)and 1(3.4%) from CHX gel and methylated spirit

as those who did not violate the study protocol. The dif-

groups respectively violated study protocol. In addition,

ference in the efficacy and the 95% confidence interval

1(3.4%) subject from methylated spirit group withdrew

(CI) was calculated by normal estimates of binomial

consent on day 2 for reasons unconnected to the study.

distribution.

Another3(10.3%) developed adverse events to 4% chlor-

Statisticala analysis was done using Stata 14.1 copyright

hexidine gel. These reactions were in the form of peri-

1985-2015 Stata Corp, 4905 Lake way Drive, College

umbilical bullous skin eruptions that extended to pubic

Station, Texas 77845 USA. Serial N0:301406310375

regions which were in direct contact with the gel. Bul-

Ethical and confidentiality consideration

lous fluid swabs microbiological assay were sterile.

Ethical approval was received from JUTH’S Ethics

These were therefore, excluded from final data analysis

Committee (JUTH/DCS/ADM/127/XXV/162).

but were given alternative treatment agents per study

Written informed consent was received from parents of

protocol and then followed up for safety in line with

student subjects.

Good Clinical Practice Guidelines. Their cord stumps

healed, fell off and exited the study. Twenty-seven study

subjects (93.1%) and 24(82.9%) from methylated spirit

and CHX treatment groups respectively completed the

Results

study and were available for analysis at D28. (Figure 1).

Thirty-three (64%) were male with mean birth weight

Between 1 June, 2017 and 17 July, 2017, 260 deliver-

3.7kg (CI 3.04 – 3.30).The mean enrollment temperature

was 36.7 ± 0.20 C).Mean maternal age 31.5 years CI

ies were conducted (224 in JUTH and 36 in FGH). Of

the 93 newborns screened for study,66 (71.0%) were

(29.92 – 32.99) with mean parity 2.7 CI (2.25 – 3.15).

eligible. Twenty-nine eligible subjects were allocated

See Table 1 below:

Fig 1: Study flow chart

Total Neonates screened

N = 93

Ineligible neonates

n = 27 (29.0%)

Eligible neonates

n = 66 (71.0%)

Declined consent

n = 8 (12.1%)

Total enrolled

n = 58 (87.9%)

Methylated spirit

Chlorhexidine

group n = 29

gel n = 29

1 protocol

2 protocol

violation

3Adverse events

Number who contin-

ued study by D7

Number who con-

n = 28

tinued study by D7

n = 24

1 withdrew consent

Completed study and

available for follow up

D28

n = 27

D28

n = 24

Mortality

NNS

Omphalitis

Mortality

NNS

Omphalitis

1(3.7%)

2(7.4%)

0(0%)

2(8.3%)

121

Two (7.4%) and 2(8.3%) cases of neonatal sepsis (NNS)

In contrast to reported findings, there were more cases

from methylated spirit and 4% chlorhexidine gel (CHX)

of omphalitis in the CHX compares to the methylated

spirit treatment group. Streptococcus spp . was isolated

treatment arms respectively. There were 2(8.3%) cases

of omphalitis from CHX treatment group. One study

in one study subject and Pseudomonas spp . in the other.

subject (3.7%) of neonatal mortality (NNM) was re-

They both received appropriate antibiotic therapy. Con-

corded from methylated treatment. This subject devel-

versely, there were comparable proportions of neonatal

oped severe jaundice, presumably from G6PD defi-

sepsis (NNS) in both treatment arms, respectively. Thus,

ciency and died on the D3 of study. Parents declined

suggesting that, 96% alcohol could be a safe alternative

autopsy.

when CHX is unavailable.

Mortality rates in the methylated spirit treatment group

The mean cord separation time in (days) in the methy-

was high compared to the CHX group. This study sub-

lated spirit and CHX gel treatment groups were 7.96 ±

ject died on day 3 from severe neonatal jaundice, pre-

4.07, (CI 6.28 – 9.64) and 6.43 ± 3.13, CI (5.08 – 7.79)

sumably of G6PD deficiency.

respectively, p= 0.078.

One-tenths of study subjects in the CHX treatment

group developed adverse reactions. These adverse reac-

tions manifested as bullous eruptions on anterior ab-

dominal wall around the umbilical stumps and on the

Discussion

pubis areas which were in contact with CHX gel. Skin

and bullous fluid swab microbiological investigations

Within the limitations of a short report and small sized

were sterile. They were therefore, given alternative

dataset, the mean cord separation time in the methylated

agents (methylated spirit) to clean the cord stump. No

spirit treatment group was longer compared to the CHX

recorded cases of anaphylactic reactions as reported

from previous studies.

gel treatment group. The difference was not statistically

significant. Mean cord separation time in the methylated

spirit group was shorter than 9.5 ± 3.8 days but longer

than 4.54 ±1.846 days reported from Ibadan and Kano

respectively. The differences in the mean cord separa-

Conclusions

tion time in studies cited above may be due to differ-

ences in the instrument used in the studies. Both studies

Methylated spirit and 4% CHX gel have comparable

cited above relied heavily on recall information from

umbilical stump treatment efficacies. Methylated spirit

respondents which could have potentially compromised

could be a safe alternative in clinical settings where

the exact details of cord care pattern and the precise

CHX gel is unavailable and or with unsure safety pro-

strength of alcohol based agents that were used by care-

file.

givers, compared to the present study which 96% alco-

hol applied two hourly intervals were used as a com-

Limitations of the study

parator treatment group.

The small sized dataset could not favor advanced statis-

However, our find in the CHX group was comparable

tics to compare several perinatal factors that may poten-

with 6.41 and 6.90 days reported by Mousa at al and

tially influence the outcomes of interest.

respectively. Similar to other reports,

Mullany et al

10,11

male study subjects in the methylated spirit treatment

group appeared to have shorter cord separation time.

Conflict of interest: None

This find contrasted those in the CHX treatment group.

Funding: None

It also sharply contrasted earlier reports from Kano in

which, it clearly showed no significant sex difference in

cord separation time. The mechanisms for umbilical

cord separation is not completely understood. It is

Acknowledgements

thought that, the umbilical cord dries and becomes

mummified. A zone of demarcation between the normal

Dr. Kajo Ioramo made substantial contribution in data

skin of the anterior abdominal wall and the drying um-

collection and follow up. The PHC offices of Jos North

bilical cord stump is formed. This pathophysiologic

and Jos South Local Government Areas of Plateau State

process is consistent with histological section that

provided 4% Chlorhexidine gel for the study.

clearly shows polymorphonuclear leukocyte infiltrates at

this zone.

12, 13, 14

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