ArticlesEffect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial
Introduction
Infections and complications of prematurity are directly responsible for more than half of all neonatal deaths, and low birthweight is the single most important indirect factor.1 Preterm very low birthweight infants (<1500 g) are particularly vulnerable; they have mortality rates of 50% and upwards in both hospital and community settings in developing countries,2 and account for 25% of all deaths in low birthweight infants.3 Despite decades of research, little progress has been made in preventing the birth of underweight babies.4 Moreover, there are few options for management of serious neonatal bacterial infections in developing countries, and the effectiveness of antibiotics is increasingly threatened by the emergence of resistance. Thus, there is an urgent need to develop simple, effective measures to prevent neonatal infections, particularly in high-risk very low birthweight infants.
An important point of entry for invasive pathogens could be skin with compromised barrier function.5, 6, 7 Organisms that normally inhabit the skin are the major agents of sepsis in very low birthweight infants in developed countries,8 and invasion of pathogens into and through keratinocytes, the main cell type of the skin, has been documented.5, 6, 9 The skin of preterm infants lacks vernix, a protective cutaneous biofilm with antimicrobial properties10 and, as prematurity becomes more extreme, the skin barrier is increasingly immature, easily damaged, and functionally compromised,11 with various adverse consequences leading to increased morbidity and mortality.5, 7 In developing countries, skin barrier function might be further compromised by malnutrition,12 and high environmental loads with virulent pathogens compound the situation.13
Topical emollient therapy to improve the function of the skin as a barrier during the first days and weeks of life, when it is most highly compromised and risk for mortality is greatest, is a promising strategy for improving neonatal outcomes in developing countries.14, 15 When exposed to the extrauterine environment and provided with appropriate metabolic building blocks, even the highly compromised skin barrier of an extremely preterm infant will mature rapidly over the first few weeks of life.16, 17, 18 Epidermal keratinocytes can metabolise lipids derived from topically applied emollients because of a fatty acid transporter on their surface. The cells then use the lipids to form a functional epidermal barrier.16 Choice of emollient is essential, however, since some oils—eg, those that contain essential fatty acids, particularly linoleic acid—increase skin barrier function,14, 19 whereas others—eg, mustard oil, which is used almost universally in traditional oil massage of newborn babies in south Asia20, 21—could be toxic and damage the integrity of the skin barrier.14
Epidermal barrier-enhancing emollients decrease transepidermal water loss,22, 23, 24 improve the overall condition of the skin,22, 25 and minimise injury.25 They have no effect, however, on skin flora22, 25 and have variable effects on incidence of nosocomial infections in preterm very low birthweight infants in developed countries.22, 26, 27 In developing countries, topical therapy with natural oils improves thermoregulation and growth of newborn children28, 29, 30 and, according to the results of a small, randomised controlled trial in Egypt,31 topical application of sunflower seed oil can more than halve the incidence of nosocomial infections in preterm very low birthweight infants. Our aim was, therefore, to ascertain whether the incidence of invasive infections would be reduced in preterm babies born in Bangladesh treated with topical application of either sunflower seed oil—a natural and widely available oil—or Aquaphor—a proprietary ointment with promising yet variable effect on neonatal outcomes.22, 26, 27
Section snippets
Participants
Between December, 1998, and July, 2003, we enrolled newborn babies admitted to the special care nursery at Dhaka Shishu Hospital, Bangladesh. The hospital is the largest tertiary-level paediatric hospital in the country, but has no maternity ward; thus, all patients were born elsewhere. About 80% of patients admitted to the hospital are poor by Bangladeshi standards, and prevalence of maternal malnutrition and low birthweight are among the highest in the world.
Newborn (⩽72 h old) preterm (<33
Results
Figure 2 shows the trial profile. 11% (497 of 4542) of patients admitted to the special care nursery were eligible. 13% of those enrolled left the hospital before being discharged, typically because of concerns about separation from family—eg, mother in hospital elsewhere, since none of the babies were born at Dhaka Shishu Hospital, or the family lived some distance away, since the hospital serves as a referral centre for the whole of Bangladesh. Patients who left were similar across the three
Discussion
Our findings confirm those of a smaller study31 we did in Egypt, and show that topical treatment with sunflower seed oil reduces the incidence of nosocomial infections in very low birthweight infants admitted to hospital. Aquaphor, which is less readily available and more expensive than sunflower seed oil, does not significantly reduce the risk of infection. Both emollients did, however, have a greater, and significant, effect in patients at highest risk of infection (those weighing <1250 g)
References (43)
- et al.
Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India
Lancet
(1999) - et al.
Nutritional interventions during pregnancy for the prevention or treatment of impaired fetal growth: an overview of randomized controlled trials
J Nutr
(2003) - et al.
Neonatal skin care
Pediatr Clin N Am
(2000) - et al.
Surface colonization with coagulase-negative staphylococci in premature neonates
J Pediatr
(1989) Neonatal bacterial infections in developing countries: strategies for prevention
Semin Neonatol
(1999)- et al.
Optimization of physiological lipid mixtures for barrier repair
J Invest Dermatol
(1996) - et al.
Development of skin barrier function in premature infants
J Invest Dermatol
(1998) - et al.
Ontogeny of the epidermal permeability barrier
J Invest Dermatol Symp Proc
(1998) - et al.
Topical ointment therapy benefits premature infants
J Pediatr
(1996) - et al.
Transepidermal water loss: the signal for recovery of barrier structure and function
J Lipid Res
(1989)