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

Abstract

Background: 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.

Methods and findings: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT03079388.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: DTH, KS, PL, MCG, JW and MJM received research support from the Children’s Investment Fund Foundation and Hickey Family Foundation. DTH receives support from National Institute of Diabetes and Digestive and Kidney Diseases under Award Number T32 DK077653.

Figures

Fig 1. CONSORT flow diagram.

“Lost to follow-up” refers to individuals who were not seen at the time point indicated and subsequently never seen again. “Visit data unavailable” refers to individuals who were not seen at the time point indicated but subsequently seen. Deaths are reported as additional deaths between each time point.

Fig 2. Kaplan–Meier survival estimates.

Shown is the incidence of death among offspring assigned to the intervention group and those assigned to the standard of care. Values were calculated with the use of Kaplan–Meier methods and compared with Mantel–Haenszel test. Panel A demonstrates the survival curve for perinatal and neonatal mortality. Panel B demonstrates infant mortality from birth until 6 months of life.