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J Matern Fetal Neonatal Med, Early Online: 14
! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.900037

ORIGINAL ARTICLE

The effect of topical ointment on neonatal sepsis in preterm infants

Aydin Erdemir1, Zelal Kahramaner1, Yelda Yuksel2, Hese Cosar1, Ebru Turkoglu1, Sumer Sutcuoglu1, Esra Arun Ozer1,
and Sukran Kose3
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Tepecik Education and Research Hospital, Neonatology Clinic, Yenisehir, Izmir, Turkey, 2Salihli State Hospital, Department of Dermatology,
Salihli, Manisa, Turkey, and 3Tepecik Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Yenisehir,
Izmir, Turkey
Abstract

Keywords

Objective: To investigate the effects of topical ointment therapy on neonatal sepsis in

premature infants.
Methods: A total of 197 premature infants  34 weeks gestation were randomized to receive
topical ointment (Aquaphor Original Emollient) or routine skin care group. Skin cultures were
obtained on 3th, 7th and 14th day and blood cultures were obtained if sepsis was suspected
clinically. Data included the maternal and neonatal characteristics, factors affecting the risk of
sepsis and neonatal outcomes of both groups were collected.
Results: There were no significant differences in terms of gestational age, birth weight, gender,
mode of delivery, multiple pregnancy and receiving antenatal corticosteroids between the
study and control group. No statistically significant difference was found in the prevalence of
sepsis, in the positive skin culture rates at any follow-up and in terms of the neonatal
morbidities including patent ductus arteriosus and necrotizing enterocolitis between the
groups. Although the rate of death was higher in the topical ointment group, no statistically
significant difference was found between the groups.
Conclusions: Our data suggests that applying topical ointment during the first 2 postnatal
weeks did not affect the risk of neonatal sepsis in preterm infants, although it changed the
bacterial flora on the skin compare to the routine care group.

Emollient therapy, neonatal sepsis, preterm

infant, skin care, topical ointment

Introduction
Although advanced neonatal care enables, sepsis continues to
be an important cause of morbidity and mortality among
infants, especially those born prematurely. The reported
incidence of neonatal sepsis is about 1030%, and up to
40% in neonates with birth weight less than 1000 g [1,2].
Immaturity of immune system, invasive supportive care such
as parenteral nutrition, indwelling intravascular catheters,
endotracheal intubation, immature barrier function of the skin
and prolonged hospital stay increase the susceptibility of
preterm infants to infections [3,4].
The skin of preterm infant is immature and fragile due to
the reduced development of the stratum corneum [5]. Poor
epidermal barrier function is ineffective to prevent invasion
by colonizing bacteria. Enhancement of the skin barrier by
topical emollient therapy during the neonatal period has been
shown to reduce transepidermal water and electrolyte loss,
conserve heat and energy, and to reduce the incidence of

Address for correspondence: Esra Arun Ozer, Associate Professor in

Pediatrics, MD, Izmir Tepecik Education and Research Hospital,
Neonatology Clinic, Yenisehir, Izmir, Turkey. Fax: + 90 232 4330756.
E-mail: eozer@deu.edu.tr

History
Received 2 October 2013
Revised 23 October 2013
Accepted 26 October 2013
Published online 9 April 2014

sepsis [69]. Thus, applying ointment to the skin may protect

against skin breakdown and prevent the spreading microbiological flora into the blood stream. However, the largest
multicenter study enrolled 1191 preterm infants demonstrated
that topical emollients improved neonatal skin condition, but
were associated with an increased risk of nosocomial bacterial
sepsis and coagulase-negative staphylococcal infections [10].
In this study, we aimed to investigate whether the
application of topical ointment would reduce the risk of
neonatal sepsis by enhancing the skin barrier or increase the
sepsis by changing the colonization of skin.

Materials and methods

Study population
This prospective, randomized, controlled study was conducted at the Neonatology Clinic of Tepecik Training and
Research Hospital (level III neonatal intensive care unit), in
Izmir, Turkey, between September 2010 and September 2012.
A total of 197 premature infants who were 34 weeks
gestation and 24 h old at the time admission were included
in the study. Gestational age was based on the last menstrual
period. If unknown, new Ballard scoring system or prenatal
ultrasonography estimates were used [11]. Exclusion criteria
were admission after the 24 h of age, those with major

A. Erdemir et al.

congenital anomalies, hydrops fetalis, congenital skin anomalies, congenital infection of the skin and sepsis. The study was
approved by ethics committee of Izmir Tepecik Education and
Research Hospital and informed consent was obtained from
all parents before study entry.

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Study design
Enrolled infants were randomized to receive either topical
ointment (Aquaphor Original Emollient Ointment, Beiersdorf
Inc, Norwalk, CT) or routine skin care using sealed, opaque
envelopes. Emollient was applied by nurses to the entire body
surface except the scalp and face once a day through the 14th
day of life. A 1.5 ml/kg of ointment was used to each neonate in
sterile syringes and nurses were trained for proper application
to minimize the skin injury and contamination. The routine
skin care group received no application of ointments. After
baseline blood cultures were obtained, a broad-spectrum
antibiotic therapy (ampicillin and amikacin) was administered
initially to all infants. The infants were studied for a period of
3 weeks. Skin swabs were obtained from the region of axilla for
cutaneous flora by a modified swab-wash method [6]. Skin
cultures were taken routinely on day 3, 7, and 14 of
hospitalization. Blood cultures were obtained if sepsis was
suspected clinically. Bacterial pathogens were identified in
cultures using standard techniques [12].
Neonatal sepsis
Infants with no sepsis on admission and who had clinical
symptoms and/or laboratory findings that were suggestive of
systemic infection without bacteriologic confirmation were
diagnosed as clinical sepsis. The clinical symptoms included
lethargy, feeding intolerance, hypoglycemia or hyperglycemia, poor perfusion, thermal instability, apnea, bradycardia
or tachycardia and increase in oxygen requirement or
ventilatory support.
Infants who had microorganisms isolated in blood cultures
taken on suspicion of sepsis according to the clinical signs
and/or laboratory findings were diagnosed as culture proven
sepsis [13].
Data acquisition
Clinical data including gestational age, birth weight, gender,
route of delivery, use of antenatal corticosteroids, multiple
pregnancy, maternal pregnancy diseases [preeclampsia, preterm premature rupture of membranes (more than 18 h before
delivery, PPROM), urinary tract infection], presence of
indwelling intravascular catheter, application of mechanical
ventilation, duration of parenteral nutrition, types of enteral
feeding (human milk or formula), presence of patent ductus
arteriosus (PDA) requiring treatment, necrotizing enterocolitis (classified based on Bells criteria [14], stage II or greater,
NEC), sepsis (clinically suspicious or culture positive) and
mortality were collected from the patients chart records.
Statistical analysis
Statistical analysis was performed using the Statistical
Package of Social Science (SPSS), Version 15.0 (SPSS,
Inc., Chicago, IL). Data were expressed as mean standard

J Matern Fetal Neonatal Med, Early Online: 14

deviation. Student t test and MannWhitney U test were used

for comparing mean values. A p value less than 0.05 was
considered statistically significant.

Results
A total of 197 preterm infants met entry criteria and were
enrolled in the study. Infants were randomized to two groups
(100 infants in the topical ointment group and 97 infants in
the routine skin care group). Mean gestational age and birth
weight of the preterm infants were similar in both groups and
there were no significant differences in terms of gender, mode
of delivery, multiple pregnancy and receiving antenatal
corticosteroids between the study and control group.
(p40.05) (Table 1).
Maternal pregnancy diseases which were risk factors for
neonatal sepsis and included preeclampsia and PPROM did
not differ significantly between the groups, while urinary tract
infection was higher in the control group (p 0.04) (Table 1).
Also therapeutic modalities included the placement of
indwelling intravascular catheter and the initiation of mechanical ventilation, presence of parenteral nutrition that might
increase the risk of sepsis were not significantly different
between the groups (p40.05) (Table 2). Ninety-four (94%) of
the infants was fed with human milk in the study group while
90(%93) of the infants in the control group.
Neonatal sepsis (clinical and culture proven) occurred in
41(41%) of infants in the topical ointment group and in
43(44.3%) of infants in the routine skin care group. In case of
sepsis with bacteriologic confirmation occurred in 23(23%) of
infants in the study group and in 19(19.6%) of infants in the
control group. No statistically significant difference was
Table 1. Characteristics of the study and control groups.
Topical ointment
group (n 100)

Control
group (n 97)

29.0 2.3
1240 386
54/46
18 (18)
34/66

29.2 2.4
1285 406
53/44
10 (10.3)
23/74

0.56
0.42
0.92
0.12
0.11

Gestational age (week)*

Birth weight (g)*
Gender (male/female)
Multiple pregnancy, n (%)
Delivery mode
(vaginal/caesarian)

*Values are presented as means SD.

Table 2. Factors affecting the prevalence of sepsis.

Topical ointment
Control
group (n 100) group (n 97)
Indwelling intravascular
catheter n (%)
Mechanical ventilation n (%)
Antenatal corticosteroids n (%)
Parenteral nutrition (day)y
Maternal pregnancy
diseases n (%)
Preeclampsia
PPROM
Urinary tract infection

12 (12)

8 (8.2)

0.38

77 (77)
39 (39)
15.6 4.6

69 (71.1)
31 (32)
14.7 5.0

0.34
0.30
0.21

17 (17)
14 (14)
5 (5)

17 (17.5)
21 (21.6)
13 (13.4)

0.92
0.16
0.04*

*p50.05.
yValues are presented as means SD. PROM, premature rupture of
membranes.

The effect of topical ointment in preterm infants

DOI: 10.3109/14767058.2014.900037

Table 3. Neonatal outcomes in the two groups.

Topical ointment
Control
group (n 100) group (n 97)

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Necrotizing enterocolitis n (%)

Patent ductus arteriosus
treated n (%)
Death n (%)
Neonatal sepsis n (%)
Culture positive

3 (3)
28 (28)

2 (2.1)
20 (20.6)

0.67
0.22

10 (10)
41 (41)
23 (23)

4 (4.1)
43 (44.3)
19 (19.6)

0.10
0.63
0.42

found in the prevalence of neonatal sepsis between the groups

(p40.05) (Table 3).
There was no group difference in positive skin culture rates
at any follow-up time (in the study and control group,
respectively number of positive skin cultures on 3th day, 3 and
3, on 7th day, 1 and 3, on 14th day, 4 and 4). A total of three
bacterial species (Staphylococcus aureus, Enterococcus
faecalis, coagulase-negative Staphylococcus) were isolated
in the topical ointment group and eight bacterial species
(Sphingomonas
paucimobilis,
Enterobacter
cloacae,
Enterococcus faecalis, Serratia marcescens, Candida albicans, Stenotrophomonas maltophilia, Klebsiella pneumoniae,
coagulase-negative Staphylococcus) were isolated in the
routine skin care group from skin cultures. Coagulase
negative Staphylococcus was isolated in six (75%) of the
eight positive skin culture in the treatment group and in
3 (30%) of 10 positive skin culture in the control group. None
of the blood cultures obtained on admission showed positive
results. Coagulase negative Staphylococcus was isolated in
22 (95.6%) of 23 positive blood culture in the treatment group
and in 17 (89.4%) of 19 positive blood culture in the control
group. Candida parapsilosis was isolated in a positive blood
culture of one infant in the treatment group, Staphylococcus
aureus and Klebsiella pneumoniae were isolated in positive
blood cultures of two infant in the control group. In only two
infants of cultures taken on suspicion of sepsis, skin
pathogens (coagulase-negative Staphylococcus) matched
with the blood pathogen in the treatment group while only
one infant had the same organism (coagulase-negative
Staphylococcus) on the skin and in the blood cultures in the
control group. One infant with clinical sepsis (without
bacteriologic confirmation) had a positive skin culture
(coagulase-negative Staphylococcus) in the treatment group
while three infants had positive skin cultures (Serratia
marcescens, Candida albicans and coagulase-negative
Staphylococcus) in the control group (p 029).
There was no difference in terms of the neonatal
morbidities including NEC, PDA and mortality between the
study and control groups (p40.05) (Table 3). There were no
reported adverse events as a result of topical therapy.

Discussion
The skin of preterm infants is immature and not fully formed.
The stratum corneum that functions as an epidermal barrier
becomes mature until 3234 weeks gestation. In preterm
infants, the skin matures rapidly after birth and has a
functionally mature stratum corneum by 2 weeks postnatal
age [5,1517]. An ineffective epidermal barrier can result in

excessive transepidermal water loss, skin breakdown, epidermal abrasions from removal of adhesives, be a point of entry
for microorganisms, increase the susceptibility to infections
and hence increase the morbidity and mortality [10,18].
Applying topical ointment to the immature skin may
protect the integrity of the stratum corneum and enhance
epidermal barrier function. Improved skin condition may
decrease transepidermal water loss, portals of entry for
pathogens and sepsis in preterm infants. Based on this
evidence, many trials have examined the effect of topical
ointment in premature infants. Rutter et al. [19] showed that
skin water losses were reduced by 4060% after application of
petrolatum topical agent. Lane et al. [20] randomized
34 preterm infants to receive either a water-in-oil emollient
cream or routine skin care and documented that emollient
cream moisturizer therapy of premature neonates decreases
dermatitis without changing the microbiological flora.
However, concerns have been expressed that there may be
an increase in the risk of neonatal sepsis associated with the
application of topical ointment in preterm infants. Later,
Nopper et al. [6] investigated the effect of topical ointment in
60 infants less than 33 weeks gestational age and demonstrated that topical ointment therapy decreased the transepidermal water loss, severity of dermatitis, bacterial
colonization of the skin and positive blood and cerebrospinal
fluid cultures. Similarly, Darmstadt et al. [21,22] indicated
that topical emollient therapy blocked the entry of pathogens
from the skin into the bloodstream and provided protection
against nosocomial infections in preterm infants and a trial in
Egypt showed a 54% reduction in the incidence of nosocomial
infections among preterm infants treated with topical ointment [23].
In contrast, Pabst et al. [7] reported an increased but nonsignificant risk of coagulase negative staphylococcal infection
in the ointment group. Correlatively, Edwards et al. [10]
reported a significantly increased risk of coagulase negative
staphylococcal infection in infants treated with ointment
compared to infants in the control group. They also reported
that more infants in the ointment group acquired fungal
infection than control group. Again a recent casecontrol
study suggested that extremely preterm infants weighing
51000 g who were treated with topical petrolatum ointment
were at increased risk for Candida infections [24]. Therefore,
a recent Cochrane Review, written by Edwards et al. [25]
concluded that topical emollients should not be used to treat
extremely low birth weight infants.
In this present trial, we evaluated the effect of topical
emollient therapy in preterm infants. The study group was
well matched with the control group in terms of birth weight,
gestational age, gender, multiple pregnancy and delivery
mode. We found no statistically significant difference in the
prevalence of bacterial colonization, neonatal sepsis (clinical
and/or culture proven) or any bacterial and fungal infection
between the groups. However, applying topical ointment
changed the bacterial flora on the skin compare to the routine
care group which had many more pathogens.
In this study, ttherapeutic modalities included the presence
of indwelling intravascular catheter, mechanical ventilation,
parenteral nutrition and maternal pregnancy diseases included
preeclampsia and PPROM which were risk factors for

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A. Erdemir et al.

neonatal sepsis did not differ significantly between the groups

while urinary tract infection was higher in the control group.
However, none of the blood cultures obtained on admission
showed positive results.
In this study, neonatal outcomes including PDA requiring
treatment and NEC did not differ significantly between the
groups. Similarly, two randomized controlled trials reported
no significant difference in the risk of PDA between the
topical ointment and control group [7,10].
Although the rate of death was higher in the topical
ointment group, no statistically significant difference was
found between the groups in this present study. Similarly, a
multicenter trial showed no difference in mortality rates
related to topical ointmet therapy among extremely preterm
infants [10]. In contrast, unlike our study Darmstadt et al.
[23] showed a trend toward reduced mortality rates among
preterm infants treated with topical ointment.
The drawbacks of this study include; insufficient data
about the effects of topical ointment therapy on transepidermal water loss, electrolyte balance, skin integrity and other
neonatal outcomes including intraventricular hemorrhage,
bronchopulmonary dysplasia, neurophysiological and neurodevelopmental effects.
In conclusion, we demonstrated no reduction or increase in
the risk of neonatal sepsis with prophylactic application of
ointment during the first two postnatal weeks in preterm
infants. Although applying topical ointment changed the
bacterial flora on the skin compare to the routine care group
which had many more pathogens, it did not affect the
prevalence of bacterial colonization. Additional clinical trials
with increased numbers of subjects are needed for further
evaluation of topical ointment therapy in the premature
infants.

Declaration of interest
The authors declare no conflicts of interests. The authors
alone are responsible for the content and writing of this
article.

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