Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial

Abstract

Background Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings. Methods and findings This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation. Conclusions In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility–community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function. Trial registration ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry—India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

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

“…We found that intervention with SSO therapy significantly improved the growth of newborn infants compared with usual practices by ∼1 g · kg −1 · d −1 , which is below that reported previously ( 31 , 35 , 37 , 39 , 42 , 44–54 ) and summarized in meta-analyses (1.1–2.9 g · kg −1 · d −1 ) ( 37 , 39 , 53 , 54 ) for hospitalized, very-preterm infants under efficacy conditions. Although acceptance of SSO (i.e., any use) was high in intervention infants (89%) ( 41 ), because adherence to exclusive use of SSO was low in our study—increasing by 65% from 22.6% (first quartile) to 37.2% (fourth quartile) of infants in the intervention group—per-protocol analysis was important. Per-protocol analysis revealed that infants in the intervention group who were exclusively treated with SSO as intended showed a 1.3-g · kg −1 · d −1 greater growth velocity than infants in the comparison group who exclusively received mustard oil massage.…”

“…Previously we examined the impacts of gentle massage with SSO compared with usual skin care practices in a population-based cohort of newborn infants in a rural community in Uttar Pradesh, India. We showed no overall effect on neonatal mortality but a significant 52% reduction in mortality among the subgroup of very-low-birth-weight (VLBW) infants ≤1500 g ( 41 ). Here we examine the effects of SSO treatment on the neonatal growth and morbidity of the infants in that trial.…”

“…Infants randomly assigned to the 2 study groups were comparable in baseline characteristics ( Table 1 ) ( 41 ). Briefly, mothers had a mean age of 25.4 y, most (86.7%) were Hindu and about one-third (35.9%) were from scheduled castes, one-third (33.3%) were illiterate, and most (84.8%) gave birth in a health care facility with a skilled birth attendant (83.1%).…”

“…In conclusion, considering the population-level reduction in mortality ( 41 ) along with increased growth of the subgroup of VLBW infants ( 41 ), there is an emerging evidence base for promotion of improved emollient therapy in the most highly vulnerable VLBW infants along the facility–community continuum of care. Research on integration of emollient therapy with KMC in infants born weighing <2000 g in facility and community settings is recommended ( 84 ).…”

“…The usual practice of applying mustard oil 2–4 times daily, sometimes infused with herbs and often with vigorous massage ( 7–9 ), was not intervened upon in the comparison clusters. Infants in the intervention and comparison arms were treated with emollient an average of 2.7 and 2.4 times/d, respectively ( 41 ). The intervention delivery strategy was developed through a community-centric design process and trials of improved practices aimed to ensure early and exclusive applications of SSO.…”