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.
Synopsis pending.
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.
To assess the effect of prophylactic application of topical ointment on nosocomial sepsis rates and other complications of prematurity in preterm infants.
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.
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 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.
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.
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.
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.
To assess the effect of prophylactic application of topical ointment on nosocomial sepsis rates and other complications of prematurity in preterm infants.
Randomized controlled trials comparing prophylactic application of topical ointment in preterm infants to routine skin care or as needed topical emollient ointment therapy.
Preterm infants (< 37 weeks gestation) treated within 96 hours after birth.
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.
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.
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.
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.
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).
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%.
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).
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.
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.
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.
We would like to thank Susan Hayward for preparation of this manuscript.
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.
| 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: |
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 |
| 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. |
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.
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. I. 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
Evans NJ, Rutter N. Development of the epidermis in the newborn. Biol Neonate 1986;49:74-80.
Hammarlund K, Sedin G. Transepidermal water loss in newborn infants. III. Relation to gestational age. Acta Paediatr Scand 1979;68:795-801.
Harpin VA, Rutter N. Barrier properties of the newborn infant's skin. J Pediatr 1983;102:419-25.
Nachman RL, Esterly NB. Increased skin permeability in preterm infants. J Pediatr 1971;79:628-32.
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 N. The immature skin. Br Med Bull 1988;44:957-70.
Wilson CB. Immunologic basis for increased susceptibility of the neonate to infection. J Pediatr 1986;108:1-12.
Soll RF, Edwards WH. Emollient ointment for preventing infection in preterm infants (Cochrane Review). In: The Cochrane Library, Issue 3, 1998. Oxford: Update Software.
01.01 Bacterial infection with known pathogen
01.02 Coagulase negative staphylococcal infection
01.03 Any bacterial infection
01.04 Fungal infection
01.05 Any nosocomial infection
01.06 Patent ductus arteriosus
01.07 Bronchopulmonary dysplasia
01.08 Chronic lung disease (overall) at 36 weeks adjusted age
01.09 Chronic lung disease (in survivors) at 36 weeks adjusted age
01.10 Mortality
| Comparison or outcome | Studies | Participants | Statistical method | Effect size |
|---|---|---|---|---|
| 01 Topical ointment vs control | ||||
| 01 Bacterial infection with known pathogen | 3 | 1304 | RR (fixed), 95% CI | 0.90 [0.63, 1.29] |
| 02 Coagulase negative staphylococcal infection | 4 | 1304 | RR (fixed), 95% CI | 1.31 [1.02, 1.70] |
| 03 Any bacterial infection | 4 | 1304 | RR (fixed), 95% CI | 1.19 [0.97, 1.46] |
| 04 Fungal infection | 2 | 1304 | RR (fixed), 95% CI | 1.21 [0.72, 2.02] |
| 05 Any nosocomial infection | 4 | 1304 | RR (fixed), 95% CI | 1.20 [1.00, 1.43] |
| 06 Patent ductus arteriosus | 2 | 1200 | RR (fixed), 95% CI | 1.09 [0.96, 1.23] |
| 07 Bronchopulmonary dysplasia | 1 | 1144 | RR (fixed), 95% CI | 1.03 [0.96, 1.10] |
| 08 Chronic lung disease (overall) at 36 weeks adjusted age | 1 | 1105 | RR (fixed), 95% CI | 1.02 [0.89, 1.18] |
| 09 Chronic lung disease (in survivors) at 36 weeks adjusted age | 1 | 935 | RR (fixed), 95% CI | 1.02 [0.90, 1.16] |
| 10 Mortality | 1 | 1191 | RR (fixed), 95% CI | 0.90 [0.65, 1.23] |
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 2004, Issue 1, 2004 (see www.CochraneLibrary.net 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. |
