Topical emollient therapy in the management of severe acute malnutrition in children under two: A randomized controlled clinical trial in Bangladesh

Abstract

Background: Topical emollient therapy can improve neonatal health and growth and potentially provides an additional avenue for augmenting the provision of nutrition to children with severe acute malnutrition (SAM). We hypothesised that topical treatment of hospitalised children with SAM using sunflower seed oil (SSO), in addition to standard-of-care for SAM, would improve skin barrier function and weight gain, reduce risk of infection, and accelerate clinical recovery.

Methods: We conducted a randomised, two-arm, controlled, unblinded clinical trial in 212 subjects aged 2 to 24 months who were admitted for care of SAM at the 'Dhaka Hospital' of icddr,b during January 2016 to November 2017. Enrollment was age-stratified into 2 to <6 months and 6 to 24 months age groups in a 1:2 ratio. All children received SAM standard-of-care, and the SSO group was also treated with 3 g of SSO per kg body weight three times daily for 10 days. Primary outcome was rate of weight gain over the 10-day study period. Secondary endpoints included rate of nosocomial infection, time to recovery from acute illness, skin condition score, rate of transepidermal water loss (TEWL) and C-reactive protein (CRP) level.

Results: Rate of weight gain was higher in the SSO than the control group (adjusted mean difference, AMD = 0.90 g/kg/d, 95% confidence interval (CI) = -1.22 to 3.03 in the younger age stratum), but did not reach statistical significance. Nosocomial infection rate was significantly lower in the SSO group in the older age stratum (adjusted odds ratio (OR) = 0.41, 95% CI = 0.19 to 0.85; P = 0.017), but was comparable in the younger age stratum and overall. Skin condition score improved (AMD = -14.88, 95% CI = -24.12 to -5.65, P = 0.002) and TEWL was reduced overall (AMD = -2.59, 95% CI = -3.86 to -1.31, P < 0.001) in the SSO group. Reduction in CRP level was significantly greater in the SSO group (median: -0.28) than the control group (median 0.00) (P = 0.019) in the younger age stratum.

Conclusions: Topical therapy with SSO was beneficial for children with SAM when applied as adjunctive therapy. A community-based trial with a longer intervention period is recommended to validate these results.

Trial registration: ClinicalTrials.gov: NCT02616289.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form (available upon request from the corresponding author) and declare: The following authors are current or former employees and shareholders of GlaxoSmithKline: Lindsay Kendall, Xinyi Zhu, Krishan Singh, Jonathan M. Crowther, Sunita Singh, Rachel A Gibson. All authors, external and internal, had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Copyright © 2020 by the Journal of Global Health. All rights reserved.

Figures

Figure 1

CONSORT flow diagram of the study. LAMA – left against medical advice; ITT – intention-to-treat.

Figure 2

Adjusted mean (95% CI) rate of daily weight gain by treatment group. Panel A. Children aged 2 to <6 months. Panel B. Children aged 6 to 24 months. Panel C. All children. Red circles and line represent the emollient group and blue squares and line represent the control group. The analysis method was Mixed-Model Repeated Measures adjusted for treatment, baseline weight, day, age, sex, mean food intake per day per kg, mean breast feeding frequency, baseline weight × day, treatment × day, treatment × age category, and treatment × age category × day.

Figure 3

Kaplan-Meier plot of time (days) to discharge from the acute phase, by treatment group. Panel A. Children aged 2 to <6 months. Panel B. Children aged 6 to 24 months. Panel C. For all children. Red dot lines represent the emollient group and blue lines represent the control group. Hazard ratios were calculated from a cox proportional hazards model adjusted for treatment, baseline weight-for-length z-score, age and sex.

Figure 4

Adjusted mean (95% CI) change from baseline in skin condition scores by treatment group. Panel A. Children aged 2 to <6 months. Panel B. Children aged 6 to 24 months. Panel C. For all children. Red circles and line represent the emollient group and blue squares and line represent the control group. The analysis method was Mixed-Model Repeated Measures adjusted for treatment, baseline skin appearance score, day, age, sex, baseline skin appearance score × day, treatment × day, treatment × age category and treatment × age category × day.

Figure 5

Adjusted mean (95% CI) change from baseline TEWL by treatment group. Panel A. Children aged 2 to <6 months. Panel B. Children aged 6 to 24 months. Panel C. For all children. Red circles and line represent the emollient group and blue squares and line represent the control group. The analysis method was Mixed-Model Repeated Measures adjusted for treatment, baseline TEWL, day, age, sex, baseline TEWL × day, treatment × day, treatment × age category, and treatment × age category × day.