Effects of emollient therapy with sunflower seed oil on neonatal growth and morbidity in Uttar Pradesh, India: a cluster-randomized, open-label, controlled trial

Vishwajeet Kumar, Aarti Kumar, Shambhavi Mishra, Peiyi Kan, Sana Ashraf, Shambhavi Singh, Keona J H Blanks, Michael Baiocchi, Mika Limcaoco, Amit K Ghosh, Alok Kumar, Raghav Krishna, David K Stevenson, Lu Tian, Gary L Darmstadt, Shivgarh Emollient Research Group, Sana Ashraf, Gary L Darmstadt, Peter M Elias, Amit Kumar Ghosh, Peiyi Kan, Raghav Krishna, Aarti Kumar, Alok Kumar, Vishwajeet Kumar, Hina Mehrotra, Shambhavi Mishra, Pawankumar Patil, Arti Sahu, Pramod Singh, Shambhavi Singh, Vivek Singh, David K Stevenson, Lu Tian, Ranjana Yadav, Vishwajeet Kumar, Aarti Kumar, Shambhavi Mishra, Peiyi Kan, Sana Ashraf, Shambhavi Singh, Keona J H Blanks, Michael Baiocchi, Mika Limcaoco, Amit K Ghosh, Alok Kumar, Raghav Krishna, David K Stevenson, Lu Tian, Gary L Darmstadt, Shivgarh Emollient Research Group, Sana Ashraf, Gary L Darmstadt, Peter M Elias, Amit Kumar Ghosh, Peiyi Kan, Raghav Krishna, Aarti Kumar, Alok Kumar, Vishwajeet Kumar, Hina Mehrotra, Shambhavi Mishra, Pawankumar Patil, Arti Sahu, Pramod Singh, Shambhavi Singh, Vivek Singh, David K Stevenson, Lu Tian, Ranjana Yadav

Abstract

Background: Newborn oil massage is a widespread practice. Vigorous massage with potentially harmful products and forced removal of vernix may disrupt skin barrier integrity. Hospitalized, very-preterm infants treated with sunflower seed oil (SSO) have demonstrated improved growth but community-based data on growth and health outcomes are lacking.

Objectives: We aimed to test whether SSO therapy enhances neonatal growth and reduces morbidity at the population level.

Methods: We conducted an open-label, controlled trial in rural Uttar Pradesh, India, randomly allocating 276 village clusters equally to comparison (usual care) and intervention comprised of promotion of improved massage practices exclusively with SSO, using intention-to-treat and per-protocol mixed-effects regression analysis.

Results: We enrolled 13,478 and 13,109 newborn infants in demographically similar intervention and comparison arms, respectively. Adherence to exclusive SSO increased from 22.6% of intervention infants enrolled in the first study quartile to 37.2% in the last quartile. Intervention infants gained significantly more weight, by 0.94 g · kg-1 · d-1 (95% CI: 0.07, 1.82 g · kg-1 · d-1, P = 0.03), than comparison infants by intention-to-treat analysis. Restricted cubic spline regression revealed the largest benefits in weight gain (2-4 g · kg-1 · d-1) occurred in infants weighing <2000 g at birth. Weight gain in intervention infants was higher by 1.31 g · kg-1 · d-1 (95% CI: 0.17, 2.46 g · kg-1 · d-1; P = 0.02) by per-protocol analysis. Morbidities were similar by intention-to-treat analysis but in per-protocol analysis rates of hospitalization and of any illness were reduced by 36% (OR: 0.64; 95% CI: 0.44, 0.94; P = 0.02) and 44% (OR: 0.56; 95% CI: 0.40, 0.77; P < 0.001), respectively, in treated infants.

Conclusions: SSO therapy improved neonatal growth, and reduced morbidities when applied exclusively, across the facility-community continuum of care at the population level. Further research is needed to improve demand for recommended therapy inside hospital as well as in community settings, and to confirm these results in other settings.This trial was registered at www.isrctn.com as ISRCTN38965585 and http://ctri.nic.in as CTRI/2014/12/005282.

Keywords: emollient; neonatal growth; neonatal health; neonatal morbidity; newborn growth; newborn morbidity; skin barrier.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials (CONSORT) diagram for a cluster-randomized, open-label, controlled trial of impact of emollient therapy with sunflower seed oil on growth and morbidity of neonatal infants in a population-based cohort in Uttar Pradesh, India. Adapted from Kumar et al. (41). SSO, sunflower seed oil.
FIGURE 2
FIGURE 2
Neonatal weight gain (g · kg−1 · d−1) as a function of first-visit weight (a proxy for birth weight) in infants in intervention and comparison clusters in Uttar Pradesh, India, modeled via a nonparametric restricted cubic spline regression with 4 preselected knots within each study group, adjusted for covariates as described in the Methods. n = 11,118, intervention; n = 10,834, comparison. *Indicates a statistically significant difference in weight gain between infants in the intervention vs. comparison clusters.

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