A novel intervention combining supplementary food and infection control measures to improve birth outcomes in undernourished pregnant women in Sierra Leone: A randomized, controlled clinical effectiveness trial

Authors: HENDRIXSON, DAVID TAYLOR - Washington University; SMITH, KRISTIE - Washington University; LASOWSKI, PATRICK - Washington University; CALLAGHANGILLESPIE, MEGHAN - Washington University; WEBER, JACKLYN - Washington University; PAPATHAKIS, PEGGY - California Polytechnic State University; IVERSEN, PER OLE - University Of Oslo; KOROMA, AMINATA SHAMIT - The Republic Of Sierra Leone; MANARY, MARK - Children'S Nutrition Research Center (CNRC)

Submitted to: PLoS Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2021
Publication Date: N/A
Citation: N/A

Interpretive Summary: Malnutrition in pregnancy increases the risk of poor outcomes to mother and child. A clinical trial was conducted among malnourished pregnant women in Sierra Leone to test whether a combination of a special nutritious food and treatment of common infections with antibiotics improved maternal and child outcomes. Mothers receiving the food and antibiotics gained more weight, and their newborns were longer, heavier and much less likely to die in the first month of life than women receiving a standard of care regimen. These findings provide evidence of a practical measure to reduce infant mortality in impoverished settings.

Technical Abstract: Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women. This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) =23.0 cm presenting for antenatal care at one of 43 government health clinics in Western Rural Area and Pujehun districts were eligible for participation. Standard of care included a blended corn/soy flour and intermittent preventive treatment for malaria in pregnancy (IPTp). The intervention replaced the blended flour with RUSF and added azithromycin and testing and treatment for vaginal dysbiosis. Since the study involved different foods and testing procedures for the intervention and control groups, no one except the authors conducting the data analyses were blinded. The primary outcome was birth length. Secondary outcomes included maternal weight gain, birth weight, and neonatal survival. Follow-up continued until 6 months postpartum. Modified intention to treat analyses was undertaken. Participants were enrolled and followed up from February 2017 until February 2020. Of the 1,489 women enrolled, 752 were allocated to the intervention and 737 to the standard of care. The median age of these women was 19.5 years, of which 42% were primigravid. Twenty-nine women receiving the intervention and 42 women receiving the standard of care were lost to follow-up before pregnancy outcomes were obtained. There were 687 singleton live births in the intervention group and 657 in the standard of care group. Newborns receiving the intervention were 0.3 cm longer (95% confidence interval (CI) 0.09 to 0.6; p = 0.007) and weighed 70 g more (95% CI 20 to 120; p = 0.005) than those receiving the standard of care. Those women receiving the intervention had greater weekly weight gain (mean difference 40 g; 95% CI 9.70 to 71.0, p = 0.010) than those receiving the standard of care. There were fewer neonatal deaths in the intervention (n = 13; 1.9%) than in the standard of care (n = 28; 4.3%) group (difference 2.4%; 95% CI 0.3 to 4.4), (HR 0.62 95% CI 0.41 to 0.94, p = 0.026). No differences in adverse events or symptoms between the groups was found, and no serious adverse events occurred. Key limitations of the study are lack of gestational age estimates and unblinded administration of the intervention. In this study, we observed that the addition of RUSF, azithromycin, more frequent IPTp, and testing/treatment for vaginal dysbiosis in undernourished pregnant women resulted in modest improvements in anthropometric status of mother and child at birth, and a reduction in neonatal death. Implementation of this combined intervention in rural, equatorial Africa may well be an important, practical measure to reduce infant mortality in this context.