Home > Health & Research > Health Education Campaigns & Programs > Cochrane Neonatal Review > Topical ointment for preventing infection in preterm infants

Topical ointment for preventing infection in preterm infants

Skip sharing on social media links
Share this:

Authors

Conner, JM, Soll RF, Edwards WH

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs


Dates

Date edited: 25/11/2003
Date of last substantive update: 24/07/2003
Date of last minor update: 23/10/2003
Date next stage expected 30/05/2005
Protocol first published:
Review first published:

Contact reviewer

Jeanette M. Conner, PhD, MS

Administrator of Clinical Trials
Vermont Oxford Network
33 Kilburn St.
Burlington
Vermont USA
05401
Telephone 1: 802-865-4814 extension: 210
Facsimile: 802-865-9613

E-mail: jeanette@vtoxford.org

Contribution of reviewers

J. Conner updated search strategy, excerpted data from studies and drafted the revised review. R. Soll and W. Edwards wrote the original review, checked data from identified studies and reviewed update.

Sources of Support

Internal sources of support

  • None noted.

External sources of support

  • None noted.

What's new

This review updates the previously published review titled "Emollient ointment for preventing infection in preterm infants", The Cochrane Library, Issue 3, 1998 (Soll 1998).

The updated review includes data from two additional randomized trials (Pabst 1999, Edwards 2001). Additional outcomes are noted including fungal infection, patent ductus arteriosus, bronchopulmonary dysplasia, and chronic lung disease. Results and conclusions have changed with inclusion of two more randomized trials.

Dates

Date review re-formatted: 04/09/1999
Date new studies sought but none found: / /
Date new studies found but not yet included/excluded: / /
Date new studies found and included/excluded: / /
Date reviewers' conclusions section amended: / /
Date comment/criticism added: / /
Date response to comment/criticisms added: / /

Synopsis

  • Synopsis pending

Abstract

Background

Nosocomial sepsis is a frequent and serious complication of premature infants. The increased susceptibility of ELBW infants to infection has been attributed to less effective immune function compared to mature newborns and the invasive nature of necessary supportive care. Breakdown of the barrier function of the skin may be an additional risk factor for nosocomial sepsis.

Objectives

To assess the effect of prophylactic application of topical ointment on nosocomial sepsis rates and other complications of prematurity in preterm infants.

Search strategy

Searches were made of the Cochrane Central Registry of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), Ovid DC MEDLINE through June 2003, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language.

Selection criteria

Randomized controlled trials which compared the effect of prophylactic application of topical ointment to routine (standard) skin care or as needed topical therapy in preterm infants are included in this review.

Data collection & analysis

Data regarding clinical outcomes including infection [including any bacterial infection, bacterial infection with a known pathogen, coagulase negative staphylococcal infection, fungal infection, and any nosocomial infection (bacterial or fungal)], patent ductus arteriosus, oxygen requirement at 28 days, chronic lung disease and mortality were excerpted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group.

Main results

Four randomized controlled trials were identified. All four studies reported improved skin condition in infants treated with prophylactic topical ointment (results not reported here).

All four studies reported on the incidence of any nosocomial infection, fungal infection and coagulase negative staphylococcal infection. Infants treated with prophylactic topical ointment are at increased risk of coagulase negative staphylococcal infection (typical relative risk 1.31, 95% CI 1.02, 1.70; typical risk difference 0.04, 95% CI 0.00, 0.08); and any nosocomial infection (typical relative risk 1.20, 95% CI 1.00, 1.43; typical risk difference 0.05, 95% CI 0.00, 0.09). A trend toward increased risk of any bacterial infection was found in infants treated with prophylactic topical ointment (typical relative risk 1.19, 95% CI 0.97, 1.46; typical risk difference 0.04, 95% CI -0.01, 0.08). There was no significant difference found in the risk of bacterial infection with a known pathogen, fungal infection, or other complications related to prematurity.

Reviewers' conclusions

Prophylactic application of topical ointment increases the risk of coagulase negative staphylococcal infection and any nosocomial infection. A trend toward increased risk of any bacterial infection was noted in infants prophylactically treated. Topical ointment should not be used routinely in preterm infants.

[top]

Background

Nosocomial sepsis is a frequent and serious complication of premature infants. The increased susceptibility of ELBW infants to infection has been attributed to less effective immune function compared to mature newborns (Wilson 1986). The skin of preterm infants is immature and ineffective as an epidermal barrier (Rutter 1988; Evans 1986; Hammarlund 1979). In normal development, the stratum corneum, which is responsible for epidermal barrier function, does not become functionally mature until 32-34 weeks gestation (Rutter 1988; Evans 1986; Nachman 1971). Acceleration of the maturation process occurs after birth, with even the most preterm infants having a functionally mature stratum corneum by two weeks postnatal age (Harpin 1983). Poor epidermal barrier function leads to significant disturbances in temperature regulation and water balance.

Topical ointment therapy may enhance epidermal barrier function by protecting the stratum corneum, leading to improved skin integrity and less risk of nosocomial infection. It has been postulated that breakdown of the already developmentally compromised epidermal barrier of the preterm infant may serve as a point of entry for bacterial organisms leading to nosocomial infection, and that the application of an emollient ointment may serve as a protective barrier that enhances skin integrity and epidermal maturation (Pickens 2000). Few risks have been previously reported with the use of topical ointment. Concern has been expressed that ointment therapy may complicate use of adhesives needed to secure intravenous catheters or endotracheal tubes.

The following analysis is a systematic review of randomized controlled trials that compare prophylactic application of topical ointment in preterm infants to routine skin care or as needed application of topical ointment.

Objectives

To assess the effect of prophylactic application of topical ointment on nosocomial sepsis rates and other complications of prematurity in preterm infants.

Criteria for considering studies for this review

Types of studies

Randomized controlled trials comparing prophylactic application of topical ointment in preterm infants to routine skin care or as needed topical emollient ointment therapy.

Types of participants

Preterm infants (< 37 weeks gestation) treated within 96 hours after birth.

Types of interventions

Infants randomized to prophylactic application of topical ointment compared to infants receiving routine (standard) skin care, which may include application of topical ointment for treatment of dermatitis.

Types of outcome measures

Outcomes of interest include:
  1. bacterial infection with known pathogen
  2. coagulase negative staphylococcal infection
  3. any bacterial infection
  4. fungal infection
  5. any nosocomial infection
  6. patent ductus arteriosus
  7. bronchopulmonary dysplasia
  8. chronic lung disease and
  9. mortality. Specific definitions used in the review are noted below:

Bacterial Infection with known pathogen: single blood or CSF culture positive for pathogenic bacterial organism, excluding coagulase negative staphylococcus (with associated symptoms and/or intention to treat with systemic antibiotics) after day 2 of life.

Coagulase Negative Staphylococcal Infection: single blood or CSF culture positive for coagulase negative staphylococcus or staph epidermidis.

Any Bacterial Infection: single blood or CSF culture positive for any pathogenic bacterial organism including coagulase negative staphylococcus or staph epidermidis.

Fungal Infection: single blood or CSF culture positive for any fungal organism (with associated symptoms and/or intention to treat with systemic antifungal agents and/or intention to remove central line).

Any Nosocomial Infection: single blood or CSF culture positive for any bacterial or fungal organism (with associated symptoms and/or intention to treat with systemic antibiotics or antifungal agents).

Patent Ductus Arteriosus (PDA): presence of hemodynamically significant patent ductus arteriosus.

Bronchopulmonary Dysplasia (BPD): oxygen requirement at 28 days of life.

Chronic Lung Disease (CLD): oxygen requirement at 36 weeks adjusted age. Chronic Lung Disease in Survivors: of those infants that survived, oxygen requirement at 36 weeks adjusted gestational age.

Neonatal Mortality: death due to any cause prior to day 28 of life.

Search strategy for identification of studies

Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), Ovid DC MEDLINE (MeSH terms: emollient, ointment; limits: age groups, all infants birth to 23 months; publication types, clinical trial) through June 2003, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants and journal handsearching in the English language.

[top]

Methods of the review

For included studies, information was collected regarding the method of randomization, blinding, drug intervention, stratification, and whether the trial was single or multicenter. Information regarding trial participants including gestational age, age at study entry, and other inclusion or exclusion criteria was noted. Information on clinical outcome including infection (including bacterial infection, coagulase negative staphylococcal infection, any bacterial infection, fungal infection, and any nosocomial infection), patent ductus arteriosus, bronchopulmonary dysplasia, chronic lung disease, and mortality was excerpted from the trials identified.

Description of studies

Four trials were identified that met inclusion criteria for review: Lane 1993, Nopper 1996, Pabst 1999, Edwards 2001. Details of the studies are given in the "Characteristics of Included Studies" table and references.

Lane randomized 34 neonates between 29 and 36 weeks gestation to receive either twice daily treatment with a water-in-oil emollient ointment (Eucerin Creme, Beiersdorf, Inc.) or routine skin care (Lane 1993). The investigators measured skin condition, fungal cultures and quantitative bacterial cultures twice a week. A subset of the enrolled subjects had evaluation of transepidermal water loss (using a EP1 Evaporimeter).

Nopper randomized 60 preterm infants gestational age < 33 weeks to receive 1.5 ml of preservative-free emollient ointment (Aquaphor Ointment, Beiersdorf Inc.) applied every 12 hours for two weeks or to a control group who received routine skin care with as needed application of water-in-oil emollient ointment (Eucerin, Beiersdorf, Inc.) (Nopper 1996). These investigators measured temperature, transepidermal water loss (EP1, Evaporimeter), fluid intake, weight, skin condition (skin score reflecting degree of clinical dermatitis), and microbiologic status (including surveillance skin cultures, and blood and CSF cultures as indicated).

Pabst randomized 19 preterm infants of gestational age 26 to 30 weeks to receive either topical ointment (Aquaphor Ointment, Beiersdorf Inc.) applied twice daily for two weeks or standard skin care (Pabst 1999). These investigators measured skin condition (skin score reflecting degree of clinical dermatitis), fluid requirements (ml/kg/day and serum sodium concentrations), and skin surveillance cultures.

Edwards conducted a large multicenter randomized trial of 1191 extremely low birth weight infants of birth weight 501-1000 grams who were randomized to receive a measured dose of preservative-free emollient ointment (Aquaphor Ointment, Beiersdorf Inc.) applied every 12 hours during the first two weeks of life compared to a control group who received routine skin care with as needed application of preservative-free emollient ointment (Aquaphor Ointment, Beiersdorf Inc.) for severe dermatitis (Edwards 2001). These investigators measured mortality, proven and suspect sepsis, skin condition (skin score reflecting degree of clinical dermatitis), weight, and other complications of prematurity.

Four studies were identified which did not meet inclusion criteria: Brice 1981; Rutter 1981; Campbell 2000; Wananukul 2001. A brief description of these excluded studies follows:

Brice randomized infants less than 1.5 kg to either a plastic bubble blanket or a paraffin mixture [80% soft, 20% hard paraffin (BP)] applied to the skin at six and eight hour intervals for the first two weeks of life (Brice 1981). The investigators measured temperature, weight gain/loss, mortality, and morbidity.

Rutter applied a paraffin mixture (80% soft, 20% hard paraffin) to the skin of three preterm infants to assess water loss before and after application (Rutter 1981).

Campbell evaluated risk factors in extremely low birth weight infants less than or equal to 1000 g with systemic candidiasis compared to historical control infants (Campbell 2000). Topical application of white petrolatum beginning within the first 48 hours of life was one risk factor investigated.

Wananukul applied 1.5 ml of clear topical ointment (Vaseline: liquid paraffin) to the right side of the trunk and extremities of premature infants 34 weeks gestation requiring phototherapy, while the left side was not treated (Wananukul 2001). The investigators measured transepidermal water loss (Tewameter TM 210), temperature, and bilirubin levels.

The studies noted above did not meet the inclusion criteria due to ineligible intervention (Brice 1981; Rutter 1981; Wananukul 2001) or due to lack of randomized controls (Campbell 2000; Rutter 1981).

Methodological quality of included studies

Methodologic issues of the included studies are noted below:
RANDOMIZATION: Infants were allocated to assigned treatment by randomization.
BLINDING OF TREATMENT: Investigators were unblinded regarding treatment.
BLINDING OF OUTCOME ASSESSMENT: Investigators were unblinded regarding outcome assessment.
COMPLETENESS OF FOLLOW UP: Nopper notes that a significant number of infants were transferred out of the NICU before the end of the study period and did not complete the entire 14 day study period (six control infants and eight treated infants) (Nopper 1996). However, the clinical endpoints discussed in this review are based on an intention to treat analysis. Edwards had complete data on the primary outcome measure (Edwards 2001). Some secondary outcome measures are missing complete data due to transfer or discharge home prior to the secondary outcome measure. The rates of missing data on secondary outcome measures range from 1% to 13%.

[top]

Results

INFECTION:

Bacterial Infection with Known Pathogen:

All four studies reported the outcome of bacterial infection with a known pathogen (bacterial infection with a known pathogen includes all bacterial organisms except coagulase negative staphylococcus). Lane had no infants with a bacterial infection with a known pathogen in either group (Lane 1993). In Nopper's trial of 60 infants, one infant in the control group acquired bacterial infection compared to none in the prophylactic ointment group (RR 0.33, 95% CI 0.01, 7.87) (Nopper 1996). In the small study by Pabst, a decreased, but non-significant risk of bacterial infection was found in the prophylactic ointment group (RR 0.15, 95% CI 0.01, 2.76) (Pabst 1999). This was associated with two out of eight infants in the control group acquiring bacterial infection with a known pathogen, compared to none in the prophylactic ointment group. In the large trial conducted by Edwards and colleagues, no significant difference was found between the prophylactic ointment and control groups in the risk for bacterial infection with a known pathogen (RR 0.96, 95% CI 0.67, 1.38) (Edwards 2001).

In the meta-analysis of these trials, no significant difference was found among infants treated with prophylactic ointment and control infants in the risk of acquiring a bacterial infection with a known pathogen (typical relative risk 0.90, 95% CI 0.63, 1.29; typical risk difference -0.01, 95% CI -0.04, 0.02].

Coagulase Negative Staphylococcal Infection:

All four studies reported the outcome of coagulase negative staphylococcal infection. In Lane's study of 34 infants, an increased but non-significant risk of coagulase negative staphylococcal infection was found in the prophylactic ointment group (RR 3.0, 95% CI 0.13, 68.84) (Lane 1993). Pabst also reported an increased but non-significant risk of coagulase negative staphylococcal infection in the prophylactic ointment group (RR 3.75, 95% CI 0.20, 68.89) (Pabst 1999). In the trial by Edwards, there was sufficient power to report a significantly increased risk of coagulase negative staphylococcal infection in infants treated with prophylactic ointment group compared to infants in the control group (RR 1.40, 95% CI 1.08, 1.83) (Edwards 2001). Conversely, Nopper reported a decreased risk of coagulase negative staphylococcal infection in the prophylactic ointment group with eight infants acquiring coagulase negative staphylococcus in the control group compared to one in the prophylactic ointment group (RR 0.13, 95% CI 0.02, 0.94) (Nopper 1996).

In the meta-analysis of these trials, a significantly increased risk of coagulase negative staphylococcal infection was found among infants treated with prophylactic topical ointment compared to control infants (typical relative risk 1.31, 95% CI 1.02, 1.70; typical risk difference 0.04, 95% CI 0.00, 0.08).

Any Bacterial Infection:

All four studies reported the outcome of any bacterial infection (defined as all bacterial pathogens including coagulase negative staphylococcus). Nopper found a statistically significant reduced risk of any bacterial infection in the prophylactic ointment group with one infant acquiring any bacterial infection compared to eight in the control group (RR 0.13, 95% CI 0.02, 0.94) (Nopper 1996). Pabst also found a reduced risk of any bacterial infection in the prophylactic ointment group, however this was a non-significant finding (RR 0.73, CI 0.13, 4.13) (Pabst 1999). Conversely, Edwards reported increased risk of any bacterial infection in the prophylactic ointment group (RR 1.26, 95% CI 1.02, 1.56) (Edwards 2001). Lane found an increased risk of any bacterial pathogen in the prophylactic ointment group (one infant) compared to none in the control group (RR 3.0, 95% CI 0.13, 68.84), however this was a non-significant finding (Lane 1993).

In the meta-analysis of these trials, a trend was noted toward increased risk of any bacterial infection in infants treated with topical ointment (typical relative risk 1.19, 95% CI 0.97, 1.46; typical risk difference 0.04, 95% CI -0.01, 0.08).

Fungal Infection:

All four studies reported the outcome of fungal infection; however, two do not contribute data to the analysis of relative risk since no fungal infections occurred (Lane 1993; Nopper 1996). Pabst found a non-significant reduced risk of fungal infection in the prophylactic ointment group (RR 0.25, 95% CI 0.01, 5.45) (Pabst 1999). Edwards reported that more infants in the prophylactic ointment group acquired fungal infection than in the prophylactic ointment group (RR 1.28, 95% CI 0.75, 2.17), however this was a non-significant finding (Edwards 2001).

In the meta-analysis of these two trials, no significant difference was noted between groups in the risk of fungal infection (typical relative risk 1.21, 95% CI 0.72, 2.02; typical risk difference 0.01, 95% CI -0.01, 0.03).

Any Nosocomial Infection:

All four studies reported the outcome of any nosocomial infection (including any bacterial or fungal organism). Lane reported that more infants in the prophylactic ointment group acquired any nosocomial infection compared to those in the control group (RR 3.0, 95% CI 0.13, 68.84); however, this was a non significant finding (Lane 1993). Edwards also reported that more infants in the prophylactic ointment group acquired any nosocomial infection compared to those in the control group (RR 1.27, 95% CI 1.05, 1.53), a significant finding (Edwards 2001). Nopper 1996 and Pabst 1999 found a decreased risk of any nosocomial infection in infants treated with prophylactic ointment (RR 0.13, 95% CI 0.02, 0.94; and RR 0.48, 95% CI 0.10, 2.26 respectively). Nopper's findings were statistically significant for this outcome.

In the meta-analysis of these trials, an increased risk of any nosocomial infection was found in infants treated with prophylactic topical ointment compared to control infants (typical relative risk 1.20, 95% CI 1.00, 1.43; typical risk difference 0.05, 95% CI 0.00, 0.09).

OTHER COMPLICATIONS OF PREMATURITY:

Patent Ductus Arteriosus (PDA):

Two of the four studies reported the outcome of PDA. Edwards had incomplete data on seven of the treated infants and three of the infants in routine skin care group. Pabst found no significant difference in the risk of PDA between the study groups (RR 0.91, 95% CI 0.35, 2.35) (Pabst 1999). Edwards also reported no significant difference in the risk of PDA between groups (RR 1.09, 95% CI 0.96, 1.24) (Edwards 2001).

In the meta-analysis of these two studies, there was no significant difference in the risk of PDA between the study groups (typical relative risk 1.09, 95% CI 0.96, 1.23; typical risk difference 0.04, 95% CI -0.02, 0.09).

Bronchopulmonary Dysplasia:

Only one study reported on the outcome of oxygen requirement at 28 days of age (Edwards 2001). Edwards had incomplete data on this secondary outcome measure. Three infants in the treatment group had missing data, one infant died, and 23 infants transferred prior to day 28 of life. One infant in the routine skin care group had missing data, one infant died, and 18 were transferred prior to day 28 of life. These investigators found no significant difference in the need for oxygen supplementation at 28 days of age between the study groups (RR 1.03, 95% CI 0.96, 1.10).

Chronic Lung Disease (36 Weeks Adjusted Age):

One study reported on the outcome of chronic lung disease at 36 weeks adjusted age (Edwards 2001). In this study, seven of the treated infants had data missing on CLD, and 45 infants were transferred prior to 36 weeks adjusted age. Two infants in the routine skin care group had missing data and data were unavailable on 32 infants who were transferred prior to 36 weeks adjusted age. In this study, no significant difference was found in the overall risk for chronic lung disease between the study groups (RR 1.02, 95% CI 0.89, 1.18).

Chronic Lung Disease in Survivors (36 Weeks Adjusted Age):

In this same study, the outcome of chronic lung disease at 36 weeks adjusted age in survivors was reported (Edwards 2001). Edwards had incomplete data on this outcome measure. Eighty four infants in the treated group died by 36 weeks adjusted age, 79 were alive with missing data, 10 were transferred prior to 36 weeks adjusted age, and 37 were discharged home prior to 36 weeks adjusted age. In the routine skin care group, 86 infants died prior to 36 weeks adjusted age, 72 were alive with data missing, three were transferred prior to 36 weeks adjusted age, and 41 were discharged home prior to 36 weeks adjusted age. No significant difference was found in risk for chronic lung disease in survivors between the study groups (RR 1.02, 95% CI 0.90, 1.16).

Mortality (28 day):

One study reported the outcome of mortality at 28 days of age (Edwards 2001). These investigators found no significant difference in the risk of death at 28 days of age between the study groups (RR 0.90, 95% CI 0.65, 1.23).

Discussion

The skin of the preterm infant is an ineffective epidermal barrier. Daily prophylactic application of a topical emollient ointment was demonstrated to improve skin condition in all four trials (results not reported here). Daily application of a topical ointment was also found to reduce transepidermal water loss in the first six hours of life in one of the four trials, although these findings were not consistent in the two additional trials measuring fluid balance and transepidermal water loss (results not reported here). One of the studies not included in this analysis (Wananukul 2001) reported findings consistent with the Nopper study - a reduction in transepidermal water loss in infants in the first six hours of life after application of Vaseline-liquid paraffin.

The data from this analysis demonstrate that daily prophylactic application of a topical ointment in premature infants increases the relative risk of coagulase-negative staphylococcal infection by 31%, and increases the relative risk of any nosocomial infection (including bacterial and fungal organisms) by 20% in treated infants. The data also show that there is a trend toward increased risk of any bacterial infection in infants treated with prophylactic application of a topical ointment. There is no significant difference in the risk of bacterial infection with a known pathogen (excluding coagulase negative staphylococcus), fungal infection, mortality, or other complications of prematurity (PDA, CLD, BPD) in infants treated with prophylactic topical ointment compared to controls.

It is unclear what mechanism is related to the increased rate of coagulase negative staphylococcal or nosocomial infections in infants treated with topical ointment. Contamination may have occurred during the application process. The methods of topical ointment administration varied among the studies. In the Edwards study (Edwards 2001), individual tubes of ointment were administered to each treated infant daily, while in Lane's and Nopper's studies (Lane 1993; Nopper 1996), the emollient ointment was administered in sterile syringes. Pabst did not report the specific method of ointment administration. A more likely mechanism is that the topical ointment provided an environment conducive to the proliferation of bacterial organisms when applied to the fragile and immature epidermis of the premature infant.

Daily prophylactic application of a topical ointment for premature infants improves skin condition as reflected by skin score and evaporative water loss. This benefit does not outweigh the increased risks of coagulase negative staphylococcal and any nosocomial infection in compromised premature infants. Topical ointment should not be used routinely in preterm infants.

Reviewers' conclusions

Implications for practice

Prophylactic topical application of preservative-free emollient ointment has been demonstrated to improve skin condition but increases the risk of coagulase negative staphylococcal infection and any nosocomial infection in premature infants. These results are from data of three small and one large randomized clinical trial.

The practice of prophylactic application of topical ointment has not been found to be beneficial to premature infants in reducing the risk of nosocomial infection.

Implications for research

Analyses of the impact of a short duration of topical ointment on the risk of infection and the relationship to fluid balance are still required.

Acknowledgements

We would like to thank Susan Hayward for preparation of this manuscript.

Potential conflict of interest

Drs. J. Conner, W. Edwards and R. Soll were principal investigators for the Vermont Oxford Network study entitled "Neonatal Skin Care Study: The Effect of Aquaphor Original Emollient Ointment on Nosocomial Sepsis Rates and Skin Integrity in Infants of Birthweight 501-1000 grams". The study was supported in part by a grant from Beiersdorf, Inc.

[top]

Characteristics of studies

Characteristics of Included Studies

Study Methods Participants Interventions Outcomes Notes Allocation concealment
Edwards 2001 Multicenter
Blinding of randomization: Yes
Blinding of intervention: No
Complete follow-up:
Complete for primary outcome. Incomplete follow up of certain secondary outcomes.
Blinding of outcome measurement: No
Stratification: Yes: birth weight categories (501-750 g, 751-1000g)
Preterm infants BW 501-1000g
Age < 48 hours
Expected to survive beyond 48 hours
No evidence of skin disease
No life threatening congenital anomalies
Infants randomized:
Prophylactic application: n=602
Control group (routine skin care): n=589
PROPHYLACTIC GROUP: 3-5" ribbon of preservative free ointment (Aquaphor Ointment, Beiersdorf Inc.) applied q 12h for the first 2 weeks of life.

CONTROL GROUP: Routine skin care as needed local application of Aquaphor to area of dermatitis.

Nosocomial bacterial and fungal sepsis
Mortality at 28 days
Skin Condition
Complications of prematurity
A
Lane 1993 Single center
Blinding of randomization: Yes
Blinding of intervention: No
Complete follow-up: Yes
Blinding of outcome measurement: No
Stratification: None
Preterm infants
Gestational age 29-36 weeks
Age < 24 hours
Expected to be in NICU for more than 1 week
Infants randomized:
Prophylactic application: n=17
Control group: n=17
PROPHYLACTIC GROUP:
1-1.5g of water-in-oil
emollient cream
(Eucerin Creme, Beiersdorf, Inc.)
Applied daily x 16 days

CONTROL GROUP: Routine skin care

Skin condition
Fungal cultures
Bacterial cultures
Transepidermal water loss
A
Nopper 1996 Single center
Blinding of randomization: Yes (computerized random selection)
Blinding of intervention: No
Complete follow-up: Yes
Blinding of outcome measurement: No

Stratification: None

Preterm infants
Gestational age < 33 weeks
Age < 96 hours
No evidence of skin disease
No congenital birth defect
Infants randomized:
Prophylactic application: n=30
Control group: n=30
PROPHYLACTIC GROUP:
1.5 ml preservative free ointment (Aquaphor Ointment, Beiersdorf, Inc.) applied q12h x 2 weeks

CONTROL GROUP:
Routine skin care, as needed application of water-in-oil emollient (Eucerin, Beiersdorf, Inc.)

Temperature
Transepidermal water loss
Fluid intake
Weight
Skin condition
Microbiology
A
Pabst 1999 Single center
Blinding of randomization: Yes
Blinding of intervention: No
Complete follow-up: Yes
Single center
Blinding of randomization: Yes
Blinding of intervention: No
Complete follow-up: Yes
Blinding of outcome measurement: No
Stratification: No
Preterm infants Gestational age 26-30 weeks
Age < 24 hours
Prophylactic application: n=11
Control group (routine skin care) n=8
PROPHYLACTIC GROUP: 1.5 ml of preservative free ointment (Aquaphor Ointment, Beiersdorf Inc. applied q12h x 14 days

CONTROL GROUP: Routine skin care, no use of lotions or creams.

Skin condition
Fluid requirements (daily fluid intake and urine output)
Bacterial cultures
A

Characteristics of excluded studies

Study Reason for exclusion
Brice 1981 Quasi random, comparison of paraffin mixture and thermal blankets
Campbell 2000 Case control study using historical controls to evaluate risk factors associated with systemic candidiasis. Topical ointment application of white petrolatum was used for skin care during this study period.
Rutter 1981 Non random, before and after evaluation of topical application of paraffin mixture
Wananukul 2001 Infants as own controls, comparison of topical application of Vaseline: liquid paraffin 1:1 mixture to one side of the body with no application to the other side. Outcome measure was transepidermal water loss.

[top]

References to studies

Included studies

Edwards 2001

{published data only}

Edwards WH, Conner JM, Soll RF et al. The effect of Aquaphor Original Emollient Ointment on nosocomial sepsis rates and skin integrity in infants of birth weight 501 to 1000 grams. Pediatr Res 2001;49:388A.

Lane 1993

{published data only}

Lane AT, Drost SS. Effects of repeated application of emollient cream to premature neonates' skin. Pediatrics 1993;92:415-19.

Nopper 1996

{published data only}

Nopper AJ, Horii KA, Sookdeo-Drost S, Wang TH, Mancini AJ, Lane AT. Topical ointment therapy benefits premature infants. J Pediatr 1996;128:660-69.

Pabst 1999

{published data only}

Pabst RC, Starr KP, Qaiyumi S, Schwalbe RS, Gewolb IH. The effect of application of aquaphor on skin condition, fluid requirements, and bacterial colonization in very low birth weight infants. J. Perinatol 1999;19:278-83.

Excluded studies

Brice 1981

{published data only}

Brice JEH, Rutter N, Hull D. Reduction of skin water loss in the newborn. II. Clinical trial of two methods in very low birthweight babies. Arch Dis Child 1981;56:673-75.

Campbell 2000

{published data only}

Campbell JR, Zaccaria, E, Baker CJ. Systemic candidiasis in extremely low birth weight infants receiving topical petrolatum ointment for skin care: A case-control study. Pediatrics 2000;105:1041-45.

Rutter 1981

{published data only}

Rutter N, Hull D. Reduction of skin water loss in the newborn. Effect of applying topical agents. Arch Dis Child 1981;56:669-72.

Wananukul 2001

{published data only}

Wananukul S, Praisuwana P, Kescorncam K. Effects of clear topical ointment on transepidermal water loss in jaundiced preterm infants receiving phototherapy. J Med Assoc Thai 2001;84:837-41.

* indicates the primary reference for the study

Other references

Additional references

Evans 1986

Evans NJ, Rutter N. Development of the epidermis in the newborn. Biol Neonate 1986;49:74-80.

Hammarlund 1979

Hammarlund K, Sedin G. Transepidermal water loss in newborn infants. III. Relation to gestational age. Acta Paediatr Scand 1979;68:795-801.

Harpin 1983

Harpin VA, Rutter N. Barrier properties of the newborn infant's skin. J Pediatr 1983;102:419-25.

Nachman 1971

Nachman RL, Esterly NB. Increased skin permeability in preterm infants. J Pediatr 1971;79:628-32.

Pickens 2000

Pickens WL, Warner RR, Boissy YL, Boissy RE, Hoath SB. Characterization of vernix caseosa: water content, morphology, and elemental analysis. J Invest Dermatol 2000;115:875-81.

Rutter 1988

Rutter N. The immature skin. Br Med Bull 1988;44:957-70.

Wilson 1986

Wilson CB. Immunologic basis for increased susceptibility of the neonate to infection. J Pediatr 1986;108:1-12.

Other published versions of this review

Soll 1998

Soll RF, Edwards WH. Emollient ointment for preventing infection in preterm infants (Cochrane Review). In: The Cochrane Library, Issue 3, 1998. Oxford: Update Software.

[top]

Data and analyses

01 Topical ointment vs control

Comparison or outcome Studies Participants Statistical method Effect size
01.01 Bacterial infection with known pathogen 3 1304 RR (fixed), 95% CI 0.90 [0.63, 1.29]
01.02 Coagulase negative staphylococcal infection 4 1304 RR (fixed), 95% CI 1.31 [1.02, 1.70]
01.03 Any bacterial infection 4 1304 RR (fixed), 95% CI 1.19 [0.97, 1.46]
01.04 Fungal infection 2 1304 RR (fixed), 95% CI 1.21 [0.72, 2.02]
01.05 Any nosocomial infection 4 1304 RR (fixed), 95% CI 1.20 [1.00, 1.43]
01.06 Patent ductus arteriosus 2 1200 RR (fixed), 95% CI 1.09 [0.96, 1.23]
01.07 Bronchopulmonary dysplasia 1 1144 RR (fixed), 95% CI 1.03 [0.96, 1.10]
01.08 Chronic lung disease (overall) at 36 weeks adjusted age 1 1105 RR (fixed), 95% CI 1.02 [0.89, 1.18]
01.09 Chronic lung disease (in survivors) at 36 weeks adjusted age 1 935 RR (fixed), 95% CI 1.02 [0.90, 1.16]
01.10 Mortality 1 1191 RR (fixed), 95% CI 0.90 [0.65, 1.23]

Additional tables

  • None noted.

Amended sections

Cover sheet
Abstract
Background
Objectives
Criteria for considering studies for this review
Search strategy for identification of studies
Methods of the review
Description of studies
Methodological quality of included studies
Results
Discussion
Reviewers' conclusions
Potential conflict of interest
References to studies
Other references
Characteristics of Included Studies
Characteristics of excluded studies
Characteristics of ongoing studies
Comparisons, data or analyses

Contact details for co-reviewers

Dr William H Edwards, MD

Professor of Pediatrics
Department of Pediatrics
Dartmouth-Hitchcock Medical Center
One Medical Center Drive
Lebanon
NH USA
03756
Telephone 1: 1-603-650-5828
Facsimile: 1-603-650-5458

E-mail: william.h.edwards@hitchcock.org

Dr Roger F Soll, M.D.

Professor of Pediatrics
Division of Neonatal-Perinatal Medicine
Fletcher Allen Health Care
Burgess 426
111 Colchester Ave.
Burlington
Vermont USA
05401
Telephone 1: +1-802-847-2392
Facsimile: +1-802-847-5225

E-mail: Roger.Soll@vtmednet.org


This review is published as a Cochrane review in The Cochrane Library, Issue 1, 2004 (see http://www.thecochranelibrary.com External Web Site Policy for information). Cochrane reviews are regularly updated as a new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the Review.