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.

Background Low birth weight (LBW) infants are at increased risk of morbidity and mortality. Identification of LBW may not occur in settings where access to reliable scales is limited. Mid-upper arm circumference (MUAC) may be an accessible, low-cost measure to identify LBW and vulnerable infants. Objectives We explored the validity of newborn MUAC in identifying LBW and vulnerable newborns in rural Sierra Leone. Methods This was a secondary analysis of infant data from a randomized, controlled clinical trial of a supplementary food and anti-infective therapies compared to standard care for undernourished pregnant women. Singleton live-born infants with birth measurements and 6-month survival data were included in this analysis. The primary outcome was validity of MUAC in identifying low birth weight (LBW) neonates. Secondary outcomes included validity of MUAC and head circumference (HC) in identifying WLZ ←2, LAZ ←2, neonatal mortality and mortality within the first 6 months of life. Results 1167 infants with 229 (19.6%) LBW were the study population. Birth MUAC (r = 0.817) and HC (r = 0.752) were highly correlated with birth weight. MUAC (Area-under-the-curve = 0.905, 95% CI 0.884 to 0.925) performed superior to HC (Area-under-the-curve = 0.88, 95% CI 0.856 to 0.904) in identifying LBW. The MUAC for identifying LBW was 9.6 cm(sensitivity = 0.86, specificity = 0.78). Neither MUAC nor HC reliably identified newborns with WLZ ←2 or LAZ ←2. MUAC ≤ 9.0 cm was the ideal cutoff for neonatal mortality (sensitivity = 53.3%, specificity = 89.7%; HR 9.57, 95% CI 1.86 to 49.30). Birth anthropometrics did not reliably identify infants at risk of death in the first 6-months of life. Conclusions MUAC identifies LBW infants and infants at-risk of neonatal mortality in Sierra Leone. Further evidence is needed to increase the use of newborn MUAC in community settings where scales are not available. Clinical Trial Registration: The primary trial was registered at ClinicalTrials.gov (NCT03079388).